trimethoprim--sulfamethoxazole-drug-combination and Toxoplasmosis--Cerebral

Toxoplasmic encephalitis (TE) is an opportunistic infection of people with human immunodeficiency virus (HIV) or other causes of immunosuppression. Guideline-recommended treatments for TE are pyrimethamine and sulfadiazine (P-S) or pyrimethamine and clindamycin (P-C); however, a substantial price increase has limited access to pyrimethamine. Consequently, some centers have transitioned to trimethoprim-sulfamethoxazole (TMP-SMX), an inexpensive alternative treatment. We aimed to review the evidence on the efficacy and safety of pyrimethamine-containing therapies vs TMP-SMX.. We searched for and included randomized controlled trials (RCTs) and observational studies of TE treatments, regardless of HIV status. Data for each therapy were pooled by meta-analysis to assess the proportions of patients who experienced clinical and radiologic responses to treatment, all-cause mortality, and discontinuation due to toxicity. Sensitivity analyses limited to RCTs directly compared therapies.. We identified 6 RCTs/dose-escalation studies and 26 single-arm/observational studies. Identified studies included only persons with HIV, and most predated modern antiretroviral treatment. Pooled proportions of clinical and radiologic response and mortality were not significantly different between TMP-SMX and pyrimethamine-containing regimens (P > .05). Treatment discontinuation due to toxicity was significantly lower in TMP-SMX (7.3%; 95% confidence interval [CI], 4.7-11.4; I2 = 0.0%) vs P-S (30.5%; 95% CI, 27.1-34.2; I2 = 0.0%; P < .01) or P-C (13.7%; 95% CI, 9.8-18.8; I2 = 32.0%; P = .031). These results were consistent in analyses restricted to RCT data.. TMP-SMX appears to be as effective and safer than pyrimethamine-containing regimens for TE. These findings support modern RCTs comparing TMP-SMX to pyrimethamine-based therapies and a revisiting of the guidelines.

Topics: Encephalitis; HIV Infections; Humans; Pyrimethamine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

A recent systematic literature and meta-analysis reported relative efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of toxoplasmic encephalitis (TE) in HIV-infected adults. Here, we estimated relapse rates during secondary prophylaxis with TMP-SMX, and further explored differences in relapse rates prior to introduction of highly active antiretroviral therapy (HAART) and the widespread adoption of HAART. A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials yielded 707 studies whereby 663 were excluded after abstract screening, and 38 were excluded after full review leaving 6 studies for extraction. We performed double data extraction with a third-party adjudicator. Study designs varied with only one randomized study, four prospective cohorts and one retrospective cohort. Relapse rates were transformed using the Freeman-Tukey method and pooled using both fixed-effect and random-effects meta-analysis models. The TMP-SMX relapse rate was 16.4% (95% CI = 6.2% to 30.3%) based on random-effects models. When the disaggregated pre-HAART studies (n = 4) were included, the relapse rate was 14.9% (random effects; 95% CI = 3.7% to 31.9%). Analysis of two post-HAART studies indicated a relapse rate of 19.2% (random effects; 95% CI = 2.8% to 45.6%). Comparing the relapse rates between pre- and post-HAART studies were contrary to what might be expected based on known benefits of HAART therapy in this population. Nevertheless, cautious interpretation is necessary considering the heterogeneity of the included studies and a limited number of subjects receiving TMP-SMX reported in the post-HAART era.

Topics: Anti-Infective Agents, Urinary; Chemoprevention; HIV Infections; Humans; Incidence; Recurrence; Secondary Prevention; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The objective of this study was to perform a systematic review and meta-analysis of the literature to evaluate the efficacy and safety of therapies for cerebral toxoplasmosis in HIV-infected adults. The pyrimethamine plus sulfadiazine (P-S) combination is considered the mainstay therapy for cerebral toxoplasmosis and pyrimethamine plus clindamycin (P-C) is the most common alternative treatment. Although trimethoprim-sulfamethoxazole (TMP-SMX) has potential advantages, its use is infrequent.. We searched PubMed and four other databases to identify randomized controlled trials (RCTs) and cohort studies. Two independent reviewers searched the databases, identified studies and extracted data. Risk ratios (RRs) were pooled across studies using random-effects models.. Nine studies were included (five RCTs, three retrospective cohort studies and one prospective cohort study). In comparison to P-S, treatment with P-C or TMP-SMX was associated with similar rates of partial or complete clinical response [P-C: RR 0.87; 95% confidence interval (CI) 0.70-1.08; TMP-SMX: RR 0.97; 95% CI 0.78-1.21], radiological response (P-C: RR 0.92; 95% CI 0.82-1.03), skin rash (P-C: RR 0.81; 95% CI 0.56-1.17; TMP-SMX: RR 0.17; 95% CI 0.02-1.29), gastrointestinal impairment (P-C: RR 5.16; 95% CI 0.66-40.11), and drug discontinuation because of adverse events (P-C: RR 0.32; 95% CI 0.07-1.47). Liver impairment was more frequent with P-S than P-C (P-C vs. P-S: RR 0.48; 95% CI 0.24-0.97).. The current evidence fails to identify a superior regimen in terms of relative efficacy or safety for the treatment of HIV-associated cerebral toxoplasmosis. Use of TMP-SMX as preferred treatment may be consistent with the available evidence and other real-world considerations. Larger comparative studies are needed.

Topics: Adult; Antiprotozoal Agents; Clindamycin; Cohort Studies; Female; HIV Infections; Humans; Male; Middle Aged; Pyrimethamine; Randomized Controlled Trials as Topic; Sulfadiazine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Cerebral toxoplasmosis or toxoplasmic meningoencephalitis (hereafter referred to as TE) was one of the first opportunistic infections to be described in human immunodeficiency virus (HIV) -infected patients. Treatment of TE has been relatively successful in comparison to other opportunistic infections. Prior to the introduction of highly active antiretroviral therapy (HAART), a median survival of over a year was reported for patients who could tolerate the toxicity of TE treatment. HAART is becoming increasingly widely available in sub-Saharan Africa, where the majority of HIV-infected patients live. Many patients in Africa are diagnosed with HIV only after developing opportunistic infections such as TE. Hence, the optimal management of opportunistic infections such as TE is important if the benefits of subsequently initiating HAART are to be seen.. The purpose of this review is to determine the most effective therapy for TE in HIV-infected adults. Different treatment regimens have been compared with regard to clinical and radiological response, mortality, morbidity, and serious adverse events.. A comprehensive search of relevant databases and other sources was conducted to identify relevant studies.. Randomised double-blinded trials were included.. Data were extracted using standardised forms and analysed using Rev Man 4.2.7 software.. Three trials were found to meet the inclusion criteria. Dannemann et al 1992 and Katlama et al 1996 compared pyrimethamine plus sulfadiazine (P+S) with pyrimethamine plus clindamycin (P+C). Torre 1998 compared P+S with trimethoprim-sulfamethoxazole (TMP-SMX). For the purposes of this review, clinical outcomes were analysed as complete or partial resolution vs. failure. Patients who crossed over or were lost to follow-up were analysed as failures. Dannemann et al 1992 assessed 59 patients. Five of 26 (19%) patients randomised to P+C died in the first 6 weeks compared with 2 of the 33 (6%) patients randomised to P+S (relative risk (RR) 3.17; 95% CI 0.67-15.06). Complete or partial clinical response was obtained in 12 (46.2%) patients receiving P+C vs. 16 (48.5 %) patients receiving P+S (RR 0.95; 95% CI 0.55-1.64). Katlama et al 1996 assessed 299 patients. Twenty-nine (19%) of the 152 patients randomised to P+C died compared with 22 (15%) of the 147 patients randomised to P+S (RR 1.27; 95% CI 0.77-2.11). We were unable to obtain data on the outcomes of patients who crossed over and therefore excluded these data from the analysis. Dannemann et al 1992 and Katlama et al 1996 were analysed together for the outcome of death. The two treatment arms did not differ for death (RR 1.41; 95% CI 0.88-2.28). Torre et al 1998 assessed 77 patients. There were no deaths during the study period. Twenty-eight (70%) of 40 patients randomised to TMP-SMX had a complete or partial clinical response compared with 26 (70%) of 37 patients randomised to P+S (RR 1.0; 95% CI 0.74-1.33).. The available evidence fails to identify any one superior regimen for the treatment of TE. The choice of therapy will often be directed by available therapy. Given the current evidence, TMP-SMX appears to be an effective alternative therapy for TE in resource-poor settings where P+S are not available.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Clindamycin; Humans; Meningoencephalitis; Poverty; Pyrimethamine; Randomized Controlled Trials as Topic; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Toxoplasma gondii is a ubiquitous pathogen that causes significant morbidity and mortality in immunocompromised patients. Although relatively uncommon, toxoplasmosis is increasingly recognized as a severe complication of hematopoietic stem cell transplantation. Timely and accurate diagnosis of this treatable infection is critical. PCR-based testing has become the preferred method for diagnosis, occasionally replacing tissue biopsy. This article reviews the clinical, diagnostic and therapeutic aspects of toxoplasmosis in the setting of hematopoietic stem cell transplantation and the current and future role of PCR-based testing for early detection and diagnosis.

Topics: Animals; Antibodies, Protozoan; Antiprotozoal Agents; Computer Systems; DNA, Protozoan; Forecasting; Humans; Immunocompromised Host; Mass Screening; Peripheral Blood Stem Cell Transplantation; Polymerase Chain Reaction; Premedication; Sensitivity and Specificity; Seroepidemiologic Studies; Toxoplasma; Toxoplasmosis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Toxoplasmic encephalitis (TE) is the second most common AIDS-related opportunistic infection of the CNS. It occurs in 10%-50% of patients with AIDS who are seropositive for antibodies to Toxoplasma gondii and have CD4+ T lymphocyte counts of < 100/mm3. Primary toxoplasmic infection usually is acquired by ingestion of T. gondii oocysts from soil contaminated by cat feces or by ingestion of tissue cysts present in undercooked red meats. In patients with AIDS, TE probably results from the reactivation of Toxoplasma tissue cysts that remained latent after the primary infection. Detection of IgG antibodies to Toxoplasma indicates prior infection and the possible presence of tissue cysts and, thus, risk for developing TE. A regimen of trimethoprim-sulfamethoxazole or dapsone plus pyrimethamine with leucovorin is recommended for persons infected with the human immunodeficiency virus (HIV) and who are seropositive for IgG to Toxoplasma after their CD4+ T lymphocyte counts fall to < 100/mm3. HIV-infected persons who are seronegative for IgG to Toxoplasma should be counseled to protect themselves from primary toxoplasmic infection by eating only well-cooked meats and washing their hands after outdoor activities involving soil contact; if they have a cat, they should feed it only commercial or well-cooked foods, keep it indoors, and make sure that the litter box is changed daily. HIV-infected persons who are Toxoplasma seropositive may also be advised about these preventive behavioral practices.

Topics: AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Cats; Dapsone; Drug Therapy, Combination; Encephalitis; Humans; Incidence; Leucovorin; Pyrimethamine; Recurrence; Risk Factors; Toxoplasmosis, Animal; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; United States

The scientific basis for using folinic acid in combination with the antiparasitic drugs prescribed to AIDS patients has been reviewed. In vitro and experimental data are unclear. On the basis of folinic acid metabolism and pharmacology and of clinical experience, we suggest that folinic acid should not be systematically added to the curative treatment of pneumocystosis with cotrimoxazole. Folinic acid may be added to prophylactic regimens using high-dose cotrimoxazole (i.e. 800 mg sulfamethoxazole twice a day) and in malnourished patients. It should be administered as soon as cytopenia occurs in the course of treatment. Concerning toxoplasmosis, the addition of folinic acid is recommended in doses of 10 to 20 mg/day in acute therapy and 5 to 10 mg/day in maintenance therapy. Dosage must be adjusted to the results of blood counts.

Topics: Acquired Immunodeficiency Syndrome; Drug Therapy, Combination; Folic Acid; Hematologic Diseases; Humans; Leucovorin; Opportunistic Infections; Pneumonia, Pneumocystis; Pyrimethamine; Sulfadiazine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

The preferred therapeutic regimen for Toxoplasma encephalitis (TE) is a combination of pyrimethamine and sulfadiazine, and trimethoprim-sulfamethoxazole (TMP-SMX) plus azithromycin is the widespread alternative therapeutic regimen. The synergistic sulfonamides tablet contains TMP, sulfadiazine, and SMX and hypothetically could be used for TE treatment. This study aimed to compare the efficacy and safety of synergistic sulfonamides plus clindamycin (regimen B) with TMP-SMX plus azithromycin (regimen A) for the treatment of human immunodeficiency virus (HIV) associated TE.. This was an open-labeled, multi-center randomized controlled trial recruited from 11 centers. Each recruited patient was randomly assigned to receive regimen A or regimen B for at least 6 weeks. The overall response was evaluated by assessment of the clinical response of TE-associated clinical features and the radiological response of TE-associated radiological findings. The overall response rate, clinical response rate, radiological response rate, and adverse events were assessed at 2, 6, and 12 weeks. Death events were compared between the two regimens at 6, 12, and 24 weeks.. A total of 91 acquired immunodeficiency syndrome (AIDS)/TE patients were included in the final analysis (44 in regimen A vs . 47 in regimen B). The overall response rate, which refers to the combined clinical and radiological response, was 18.2% (8/44) for regimen A and 21.3% (10/47) for regimen B at week 6. The results of clinical response showed that, in comparison with regimen A, regimen B may perform better with regards to its effect on the relief of clinical manifestations (50.0% [22/44] vs . 70.2% [33/47], P = 0.049). However, no significant differences in radiological response, mortality events, and adverse events were found between the two regimens at week 6.. Synergistic sulfonamides plus clindamycin, as a novel treatment regimen, showed no significantly different efficacy and comparable safety in comparison with the TMP-SMX plus azithromycin regimen. In addition, the regimen containing synergistic sulfonamides may exhibit advantages in terms of clinical symptom alleviation.. ChiCTR.org.cn, ChiCTR1900021195.

Topics: Acquired Immunodeficiency Syndrome; Azithromycin; Clindamycin; Encephalitis; Humans; Sulfadiazine; Sulfanilamide; Sulfonamides; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

An increased frequency of toxoplasma encephalitis, caused by Toxoplasma gondii, has been reported in AIDS patients, especially in those with CD4+ T cell counts <100 cells/μL. Several guidelines recommend the combination of pyrimethamine, sulfadiazine, and leucovorin as the preferred regimen for AIDS-associated toxoplasma encephalitis. However, it is not commonly used in China due to limited access to pyrimethamine and sulfadiazine. The synergistic sulfonamides tablet formulation is a combination of trimethoprim (TMP), sulfadiazine and sulfamethoxazole (SMX), and is readily available in China. Considering its constituent components, we hypothesize that this drug may be used as a substitute for sulfadiazine and TMP-SMX. We have therefore designed the present trial, and propose to investigate the efficacy and safety of synergistic sulfonamides combined with clindamycin for the treatment of toxoplasma encephalitis.. This study will be an open-labeled, multi-center, prospective, randomized, and controlled trial. A total of 200 patients will be randomized into TMP-SMX plus azithromycin group, and synergistic sulfonamides plus clindamycin group at a ratio of 1:1. All participants will be invited to participate in a 48-week follow-up schedule once enrolled. The primary outcomes will be clinical response rate and all-cause mortality at 12 weeks. The secondary outcomes will be clinical response rate and all-cause mortality at 48 weeks, and adverse events at each visit during the follow-up period.. We hope that the results of this study will be able to provide reliable evidence for the efficacy and safety of synergistic sulfonamides for its use in AIDS patients with toxoplasma encephalitis.. This study was registered as one of 12 clinical trials under the name of a general project at chictr.gov on February 1, 2019, and the registration number of the general project is ChiCTR1900021195. This study is still recruiting now, and the first patient was screened on March 22, 2019.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiprotozoal Agents; China; Clindamycin; Drug Therapy, Combination; Female; HIV Infections; Humans; Leucovorin; Male; Prospective Studies; Pyrimethamine; Sulfadiazine; Sulfamethoxazole; Sulfonamides; T-Lymphocytopenia, Idiopathic CD4-Positive; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; Vitamin B Complex

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Brain; Brazil; Female; HIV Infections; Humans; Male; Middle Aged; Neuroimaging; Tomography, X-Ray Computed; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The benefits of trimethoprim-sulfamethoxazole (TS) prophylaxis reported for persons living with HIV in Cote d'Ivoire are difficult to extrapolate to sub-Saharan African countries where bacterial resistance to TS is higher and cross-resistance between TS and sulfadoxine-pyrimethamine (SP) may impair SP efficacy for malaria treatment. We conducted a community-based cohort study to measure the incidence of potentially TS-preventable illnesses in Blantyre, Malawi. We found a high incidence of malaria, invasive bacterial infections, and probable bacterial pneumonias but low rates of Pneumocystis jiroveci pneumonia, isosporiasis, and Toxoplasma encephalitis. Most bacterial isolates were resistant to TS but sensitive to azithromycin, a possible alternative to TS. Clinical trials are needed to determine the role of TS or alternative regimens for prophylaxis against secondary infections among people living with HIV in sub-Saharan Africa. These should also assess benefit in patients receiving antiretroviral therapy.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Azithromycin; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Humans; Malaria; Malawi; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Toxoplasma encephalitis is the commonest cause of intracranial mass lesions in AIDS patients. Effective therapy includes pyrimethamine plus sulfadiazine, clindamycin with pyrimethamine, and co-trimoxazole. This study examines the efficacy of oral co-trimoxazole in 20 AIDS patients with toxoplasmosis and seeks to confirm the experience of Torre et al.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; Humans; Male; Prospective Studies; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

We assessed the incidence and determinants of bacteremia, pneumonia, and sinusitis/otitis in HIV-positive people receiving cotrimoxazole (CTX) or dapsone-pyrimethamine (DP) for primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis (TE) within a randomized clinical trial. In total, 244 patients were randomized: 122 were assigned to CTX and 122 to DP. In the cohort, 22 bacteremia, 63 pneumonia, and 39 sinusitis/otitis cases were observed. Incidence rates of bacteremia, pneumonia, and sinusitis/otitis as well as the 2-year probability of remaining free from any bacterial infection were not significantly different between the two groups. At multivariate analysis, the risks of developing bacteremia and pneumonia were found to be independently increased by the use of a central venous catheter (hazard ratio [HR], 4.48; p <.05 and HR, 4.13; p <.01, respectively) and by hospitalization (HR, 28.82; p <.05 and HR, 10.15; p <.05, respectively). In conclusion, CTX at the dosage employed for primary PCP/TE prophylaxis does not seem to protect against bacterial infections more than second-line DP.

Topics: Adult; Animals; Anti-Infective Agents; Bacterial Infections; Dapsone; Encephalitis; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Pneumocystis; Pneumonia, Pneumocystis; Pyrimethamine; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

A multicenter open, randomized, controlled trial was conducted to determine whether primary prophylaxis for Pneumocystis carinii pneumonia and toxoplasmic encephalitis can be discontinued in patients infected with human immunodeficiency virus type 1 (HIV-1) whose CD4+ T cell counts have increased to >200 cells/mm3 (and who have remained at this level for at least 3 months) as a result of highly active antiretroviral therapy (HAART). Patients were randomized to either the discontinuation arm (i.e., those who discontinued prophylaxis; n=355) or to the continuation arm (n=353); the 2 arms of the study were similar in terms of demographic, clinical, and immunovirologic characteristics. During the median follow-ups of 6.4 months (discontinuation arm) and 6.1 months (continuation arm) and with a total of 419 patient-years, no patient developed P. carinii pneumonia or toxoplasmic encephalitis. The results of this study strongly indicate that primary prophylaxis for P. carinii pneumonia and toxoplasmic encephalitis can be safely discontinued in patients whose CD4+ T cell counts increase to >200 cells/mm3 during HAART.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Antiprotozoal Agents; CD4 Lymphocyte Count; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Infections; HIV-1; Humans; Italy; Male; Middle Aged; Paris; Pentamidine; Pneumonia, Pneumocystis; Time Factors; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the influence of the dose of co-trimoxazole prophylaxis on the risk of toxoplasmosis in human immunodeficiency virus (HIV)-infected patients, we performed a nested case-control study of 32 patients with toxoplasmosis (case patients) and 64 patients without toxoplasmosis (control patients) who were matched by CD4 cell count and Toxoplasma gondii serostatus; these patients were from a cohort of 521 HIV-infected patients who underwent a diagnostic neuroimaging study between March 1993 and January 1997. Twenty-seven (84.4%) of 32 case patients and 33 (51.6%) of 64 control patients received low doses of co-trimoxazole, a finding associated with an adjusted odds ratio (OR) of 9.36 (95% confidence interval [CI], 2.05-42.75) and indicating 89% protective efficacy for high doses. Fifteen (46.9%) of 32 case patients and 16 (25%) of 64 control patients were exposed to rifampin (adjusted OR, 3.38; 95% CI, 1.08-10.61). These results indicate that high doses of co-trimoxazole appear to be more effective than low doses for lowering the risk of toxoplasmosis in HIV-infected patients and that rifampin therapy may reduce the efficacy of co-trimoxazole.

Topics: Adult; AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Antibiotics, Antitubercular; Case-Control Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Encephalitis; Female; HIV Infections; Humans; Male; Rifampin; Toxoplasma; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Non-viral opportunistic infections involving the central nervous system in AIDS patients most commonly result from toxoplasmic encephalitis (TE). Combination pyremethamin (pyr)/sulfadiazine (sulf) is the mainstay treatment for TE, but many patients experience severe adverse events occasionally requiring discontinuation of this antitoxoplasmic medication. This investigation assessed the effects of an open, prospective trial of alternative trimethroprim/sulfamethoxazole: cotrimoxazole (CTX) therapy for TE in AIDS patients.. The subjects were 18 AIDS patients with a first presumptive attack of TE (Group 1) and 9 relapsing patients, including 6 out of Group 1 (Group 2). We gave CTX as a therapy at the dose of 960 mg four times a day for 48 hours, then 960 mg three times a day for two weeks, followed by 960 mg twice daily until computed tomography showed complete disappearance of active TE lesions. Life-long maintenance therapy consisted to CTX 960 mg daily.. Group 1: Seventeen patients improved clinically and achieved complete resolution on computed tomography scars over a mean period of 33 days (range: 21-56). Only one patient was withdrawn from the study at day 18 due to a severe skin rash. Neither serious hematologic nor liver toxicity were observed. Under maintenance therapy, 7 patients relapsed after an average duration of 15.5 months. Relapses were precipitated either by poor compliance (5/7) or erronenous CTX protocol (2/7). Group 2: There were 15 relapses affecting 9 patients who were treated successfully with CTX. CTX was discontinued in one relapsing patient who experienced a Stevens-Johnson syndrome on day 13. This patient had previously experienced cutaneous intolerance to sulfadiazine.. A relative low dose regimen of CTX appears to be strongly efficient and safe treatment for toxoplasmic encephalitis in AIDS. Such a study is of particular interest for developing countries where TE is highly prevalent, given the wide availability of CTX which could be proposed as an economic first line therapy.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Drug Administration Schedule; Female; HIV Seropositivity; Humans; Male; Middle Aged; Patient Selection; Recurrence; Tomography, X-Ray Computed; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

We randomized 220 HIV-1-infected subjects to receive aerosolized pentamidine (300 mg/4 weeks) or orally trimethoprim-sulfamethoxazole (320-1600 mg/day) for primary prophylaxis of Pneumocystis carinii pneumonia (PCP), and evaluated PCP and toxoplasmic encephalitis (TE) occurrence and survival. Patients developing toxicity switched to the other regimen. Analysis was on intention-to-treat. At 1 year of study, we observed in the pentamidine group a non-significant excess of PCP (4 vs. 1) and TE (7 vs. 3), and a significant increased death rate (15 vs. 2). After 2 years, no significant differences were observed: adjusted RR estimates for pentamidine vs. cotrimoxazole were 1.20 (95% CI, 0.33-4.37) for PCP (6 cases vs. 5), 1.23 (95% CI, 0.46-3.29) for TE (10 vs. 8) and 1.52 (95% CI, 0.83-2.79) for death (30 vs. 18). Crossovers were more frequent in the cotrimoxazole group (41 vs. 4, P < 0.001). Aerosolized pentamidine and cotrimoxazole were equally effective in preventing PCP, and no major differences were observed in TE occurrence and survival after 2 years follow-up.

Topics: Adult; Aerosols; AIDS-Related Opportunistic Infections; Female; HIV-1; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

To investigate the efficacy and safety of three regimens for primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis (TE) and to evaluate their effect on survival in patients with HIV infection.. Randomized, open label, prospective trial.. A single Infectious Diseases Department in Italy.. HIV-infected patients (n = 197) with a CD4 count < 200 x 10(6)/l and without previous PCP or TE.. Patients were randomly assigned to receive (1) aerosolized pentamidine (AP; 300 mg monthly), (2) cotrimoxazole (CTX; 160 mg trimethoprim and 800 mg sulfamethoxazole every other day), or (3) dapsone-pyrimethamine (DP; 100 mg weekly dapsone and 25 mg biweekly pyrimethamine).. PCP, TE, death, and drug-limiting toxicity. Considering difference in PCP occurrence the trial was interrupted on June 1992. Observation was prolonged until June 1994 for TE and survival.. Intention-to-treat analysis yielded PCP rates of 10.2 per 100 person-years in the AP, 2.0 in the CTX, and 32.1 in the DP group [adjusted relative risk of DP versus CTX: 17.5; 95% confidence interval (CI), 2.2-139.6; P = 0.007]. TE rates in patients with positive Toxoplasma serology were 25.6 per 100 person-years in the AP, 8.9 in the CTX and 9.4 in the DP group. In 'on treatment' analysis, no episode of TE developed in the DP group, and rates were 34.7 per 100 person-years in the AP and 2.5 in the CTX group (AP versus CTX: P = 0.01; AP versus DP: P = 0.004). The adjusted risk of mortality for the DP group was 2.8 times that of the CTX group in the first part of the study (95% CI, 1.1-7.3; P = 0.037), and 1.8 times (95% CI, 1.1-2.9; P = 0.02) in the prolonged follow-up. No significant difference in the occurrence of serious adverse reactions was observed between the three treatment groups.. Intermittent CTX was more effective than low-dose DP and showed a slight but not significant advantage on AP for primary PCP prophylaxis. DP was associated with a shorter survival. Both CTX and DP resulted in a significant reduction in the risk of TE.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Dapsone; Encephalitis; Female; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Dapsone; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Sulfalene; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

The objective was to compare the efficacy and tolerance of monthly aerosolized pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) to prevent the first episode of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. In an open, prospective, randomized multicentric clinical trial, HIV-infected patients (n = 214) with CD4 cell counts < 200/mm3 or 20% without a history of PCP or cerebral toxoplasmosis were randomized to receive for at least 2 years aerosolized pentamidine (300 mg monthly) or low-dose daily TMP-SMX (400-80 mg). The mean follow-up was 578 days. The two groups (except for gender) were homogeneous for age, risk group for HIV infection, initial CD4+ lymphocyte count, and mean follow-up. The PCP rate per year of observation using an intent-to-treat analysis was 3.1% and 1.3% in the groups treated with pentamidine and TMP-SMX, respectively (p > 0.05). Moderate or severe clinical and biological side effects were observed in five patients on pentamidine and 33 on TMP-SMX (p < 0.05). Nineteen episodes of cerebral toxoplasmosis were diagnosed during the study. The analysis showed no significant difference in time of development of toxoplasmosis, but only one patient was actually treated with TMP-SMX. Survival was not significantly different in the two groups. Low-dose daily TMP-SMX or monthly aerosolized pentamidine effectively prevented a first episode of PCP in HIV-infected patients, but aerosolized pentamidine was better tolerated. However, TMP-SMX is less costly and should have a preventive effect for toxoplasmosis.

Topics: Adult; Aerosols; AIDS-Related Opportunistic Infections; Female; Follow-Up Studies; HIV Infections; Humans; Male; Pentamidine; Pneumonia, Pneumocystis; Prospective Studies; Survival Rate; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To compare the efficacy and tolerance of monthly aerosolized pentamidine versus cotrimoxazole versus dapsone plus pyrimethamine to prevent the initial episodes of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients.. An open randomized clinical trial.. HIV-infected patients (n = 331) with CD4 cell counts < 200 x 10(6)/l or with AIDS but without a history of PCP or cerebral toxoplasmosis (CT) were randomized to receive pentamidine (300 mg every 4 weeks), cotrimoxazole (160/800 mg 3 days a week) or dapsone plus pyrimethamine (100 and 25 mg weekly). If immunoglobulin G (IgG) antibodies to Toxoplasma were present, patients in the first two groups were randomized further to 25 mg pyrimethamine per week or to no treatment.. The mean follow-up was 313 days (range, 30-670 days). The three groups were homogeneous for age, sex, risk group for HIV infection, initial CD4 cell count and mean follow-up. PCP developed in 16 patients, with an estimated cumulative probability of 5.3% at 1 year of follow-up. The PCP rate per year of observation, using an intention-to-treat analysis, was 5.6% [95% confidence interval (CI), 0.9-10.3], 3% (95% CI, 0-6.3) and 8.3% (95% CI, 2.8-13.8) in the groups treated with pentamidine, cotrimoxazole and dapsone plus pyrimethamine, respectively (P > 0.05). Moderate or severe side-effects were observed in one patient on pentamidine, 10 on cotrimoxazole and nine on dapsone plus pyrimethamine (P < 0.05); the study drug had to be discontinued in no, 10 and six patients, respectively (P < 0.05). Neither cotrimoxazole alone nor pyrimethamine combined with dapsone or cotrimoxazole prevented initial episodes of toxoplasmosis among patients with IgG antibodies to Toxoplasma gondii.. Low-dose thrice-weekly cotrimoxazole or weekly dapsone plus pyrimethamine was not significantly worse (differences > 15% would have been detected with 90% certainty) than monthly aerosolized pentamidine in preventing a first episode of PCP in patients at high risk, but aerosolized pentamidine was better tolerated.

Topics: Adult; Aerosols; AIDS-Related Opportunistic Infections; Antifungal Agents; Dapsone; Drug Therapy, Combination; Drug Tolerance; Female; HIV Infections; Humans; Male; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Twenty-four consecutive HIV-positive patients affected by Toxoplasma gondii encephalitis received trimethoprim-sulfamethoxazole (cotrimoxazole) as acute-phase treatment. Two dosage regimens of cotrimoxazole were used: 40 mg/kg/day (12 patients) or 120 mg/kg/day (12 patients) of total compound (trimethoprim plus sulfamethoxazole). Clinical and radiological responses to treatment were evaluated, and the product-limit method for survival data analysis was used. Eighteen of 24 patients showed both a clinical and radiological response (75% response rate). There were no differences in response rates between patients receiving the two dosage regimens of cotrimoxazole. Adverse reaction consisted of leukopenia (two cases) and skin rash (three cases) which led to the discontinuation of the drug in one case. These results suggest that a randomized, controlled clinical trial should be carried out comparing cotrimoxazole versus sulfadiazine-pyrimethamine in AIDS patients with Toxoplasma gondii encephalitis.

Topics: Acquired Immunodeficiency Syndrome; Adult; Drug Eruptions; Encephalitis; Female; Humans; Leukopenia; Male; Middle Aged; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

A 16-year-old boy received an unrelated bone marrow transplant while in second remission of acute myeloid leukemia. He suffered from severe oral mucosal complications and had difficulty taking oral drugs such as sulfamethoxazole/trimethoprim (ST). Engraftment was obtained on transplant day 35, and blurred vision and headache appeared around transplant day 60. Funduscopy revealed retinal hemorrhage and macular edema, and an MRI scan of the head revealed a nodular lesion in the left putamen. Toxoplasma gondii was detected by CSF PCR, and cerebral toxoplasmosis was diagnosed. Following therapy with ST and clindamycin, the patient was administered pyrimethamine, sulfadiazine, and leucovorin. Symptoms improved promptly, and CSF PCR was negative 45 days after the start of treatment. Since the prevalence of toxoplasma antibodies increases with age, it is crucial to avoid toxoplasma reactivation by ST after hematopoietic cell transplantation in postpubescent patients.

Topics: Adolescent; Bone Marrow Transplantation; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Male; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Toxoplasma gondii is an obligate intracellular protozoan that causes toxoplasmic encephalitis (TE) in immunocompromised patients. We describe a case of a 29-year-old Japanese man presenting with headache and vomiting. He had previously been diagnosed with human immunodeficiency virus infection. Magnetic resonance imaging identified some nodules in his brain. We suspected TE and began treatment successively with parenteral trimethoprim-sulfamethoxazole (TMP/SMX) plus clindamycin. After that, we switched to pyrimethamine plus sulfadiazine (PMT/SDZ) because these drugs are the first-line treatment for TE. Because the patient experienced nausea and vomiting, PMT/SDZ was replaced with TMP/SMX, atovaquone, and clindamycin. However, the patient could not tolerate them owing to their adverse reactions. Thus, we attempted oral desensitization to TMP/SMX to treat his TE. We began desensitization with 0.4/2 mg of TMP/SMX. The patient experienced morbilliform rash and elevated aminotransferase levels. Therefore, we administered a glycyrrhizin and an antihistamine and continued the last tolerable dose until these symptoms improved. After 37 days, we achieved desensitization to 160/800 mg of TMP/SMX, and the patient's symptoms improved. After using nested-polymerase chain reaction to identify T. gondii DNA in his frozen cerebrospinal fluid, which was collected at admission, his diagnosis was confirmed as TE. This might be the first case to attempt desensitization to TMP/SMX to treat TE.

Topics: Adult; AIDS-Related Opportunistic Infections; Atovaquone; Brain; Clindamycin; Coccidiostats; Desensitization, Immunologic; Humans; Male; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Toxoplasmic encephalitis (TE) is a leading cause of brain mass lesions (BML) in human immunodeficiency viruses (HIV)-infected patients. Yet, so far, no accurate diagnostic approach for TE has been developed. Herein, we presented a case series (9 HIV-infected patients with TG confirmed by RT-PCR of BML) to assess the diagnostic value of reverse transcription-polymerase chain reaction (RT-PCR) on TE.. A total of 9 HIV-infected patients with TE confirmed by RT-PCR of BML were included in this study. Clinical data, including clinical symptoms, blood and CSF analysis, neuroimaging features, histopathological characteristics, treatment, and prognosis, were assessed in all patients. According to the results of RT-PCR of BML, all the patients received oral administration of trimethoprim-sulfamethoxazole combined with antiretroviral therapy (ART). Patients were followed up by telephone or outpatient service.. The application of RT-PCR of BML, together with conventional methods, may significantly improve the diagnostic efficiency of TE.

Topics: Adult; AIDS-Related Opportunistic Infections; Antimalarials; Brain; Female; HIV; Humans; Male; Middle Aged; Real-Time Polymerase Chain Reaction; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aftercare; Antimalarials; Antiprotozoal Agents; Atovaquone; Brain; Brain Edema; Female; Humans; Kidney Calculi; Liver Transplantation; Magnetic Resonance Imaging; Middle Aged; Pentamidine; Pneumonia, Pneumocystis; Sulfadiazine; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Ultrasonography

A 65-year-old woman with rheumatoid arthritis (RA) visited our hospital because of right facial sensory hypoesthesia. Cerebral toxoplasmosis was suspected on brain magnetic resonance imaging. We discontinued methotrexate for RA and started a sulfamethoxazole/trimethoprim (ST) mixture. Although ST treatment was interrupted because of adverse reactions, her prognosis was favorable. The Toxoplasma 18S rDNA gene was detected by nested-polymerase chain reaction (PCR) from blood and cerebrospinal fluid. Detecting the Toxoplasma 18S rDNA gene by nested-PCR is useful for the diagnosis and safer than a brain biopsy. In addition, the discontinuation of immunosuppressants may be recommended in patients compromised by those immunosuppressants.

Topics: Aged; Arthritis, Rheumatoid; DNA, Ribosomal; Female; Humans; Immunosuppressive Agents; Methotrexate; Polymerase Chain Reaction; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; Withholding Treatment

Topics: Adolescent; Adult; Aged; Aged, 80 and over; AIDS-Related Opportunistic Infections; Antiprotozoal Agents; Child; Child, Preschool; Critical Pathways; Databases, Factual; Female; Hospitalization; Humans; Infant; Infant, Newborn; Male; Middle Aged; Pyrimethamine; Retrospective Studies; Toxoplasmosis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; United States; Young Adult

Topics: Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Biopsy; Brain; Cyclophosphamide; Fever; Headache; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Magnetic Resonance Imaging; Male; Myeloablative Agonists; Polymerase Chain Reaction; Toxoplasma; Toxoplasmosis, Cerebral; Transplantation Conditioning; Transplantation, Homologous; Trimethoprim, Sulfamethoxazole Drug Combination; Vomiting

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Bacterial Agents; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; Humans; Magnetic Resonance Imaging; Male; Movement Disorders; Penicillins; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; Videotape Recording; Young Adult

The current standard treatment for cerebral toxoplasmosis (pyrimethamine/sulfadiazine) often encounters problems of poor tolerability, adverse effects, frequent dropouts and non-availability of pyrimethamine/sulfadiazine in some parts of India. We have had to use the combination of two effective alternative agents for toxoplasmosis, cotrimoxazole and clindamycin, on compassionate grounds. This retrospective observational study reports superior efficacy and better tolerability of cotrimoxazole/clindamycin compared to the recommended regimen. Primary end-point (complete response) was defined as more than 50% improvement of clinical status or more than 50% decrease in the size of brain lesions after two weeks of treatment initiation. Complete response occurred more commonly with cotrimoxazole/clindamycin than with pyrimethamine/sulfadiazine group (80% vs. 31.25%, respectively, relative risk 2.56, 95% confidence interval: 1.21-5.43). There was a trend towards higher on-treatment mortality in the pyrimethamine/sulfadiazine group in comparison to the cotrimoxazole/clindamycin (mortality rate 37.5% in pyrimethamine/sulfadiazine vs 12% in cotrimoxazole/clindamycin, p = 0.07, relative risk = 3.125, 95% confidence interval: 0.91-10.75). Overall, 62.5% (10/16) of patients on pyrimethamine/sulfadiazine suffered drug-related adverse reactions compared to 24% (6/25) on cotrimoxazole/clindamycin (p = 0.02, relative risk = 2.60, 95% confidence interval: 1.17-5.76). The commonest complication of pyrimethamine/sulfadiazine was severe thrombocytopenia with major bleeding (4/16, 25%). We propose that the new combination chemotherapy, which is widely available, effective and safe, can be used in developing countries.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Clindamycin; Female; Humans; India; Male; Middle Aged; Poverty; Pyrimethamine; Retrospective Studies; Sulfadiazine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

As the incidence of HIV infection has increased its neurological complications are being encountered in our clinical practice. Toxoplasmosis is a common cerebral opportunistic infection seen in HIV-infected patients, even though the incidence has declined with the use of antiretroviral therapy. Establishing a definitive diagnosis of cerebral toxoplasmosis is difficult in resource limited settings.. A 20 year old gentleman was referred to our institute as a case of stroke. Magnetic resonance imaging (MRI) of his brain showed multiple ill-defined and nodular enhancing lesions in bilateral supratentorial and infratentorial neuroparenchyma. Test for HIV-1 was reactive. Toxoplasma serology revealed raised IgG antibody levels. Based on the MRI features and positive toxoplasma serology a diagnosis of cerebral toxoplasmosis was made. He was treated with trimethoprim/sulfamethoxazole and pyrimethamine/ Sulfadoxine for 3 weeks. After 2 weeks of treatment, repeat MRI of brain was done which showed significant resolution of the lesions.. We are presenting this case to highlight the fact that cerebral toxoplasmosis should be considered in the differential diagnosis of multiple neuroparenchymal lesions in young individuals who present with neurological deficits.

Topics: AIDS-Related Opportunistic Infections; Antibodies, Protozoan; Brain; Drug Combinations; Humans; Immunoglobulin G; Magnetic Resonance Imaging; Male; Pyrimethamine; Serologic Tests; Stroke; Sulfadoxine; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Cerebral toxoplasmosis is a rare, potentially fatal, complication of hematopoietic cell transplantation. Early definitive diagnosis is very difficult and it may be associated with a poor prognosis. Herein, we describe a 60-year-old woman who developed cerebral toxoplasmosis after cord blood transplantation for myelodysplastic syndrome. During treatment with tacrolimus and methylprednisolone for relapsed grade 2 acute gut GVHD, fever and disturbance of consciousness occurred on day 210. Brain MRI showed multiple ring-enhancing nodular lesions in the thalamus, basal ganglia, brainstem, and subcortical white matter. Cerebrospinal fluid (CSF) assessment revealed elevations of both anti-to-xoplasma IgM and IgG, which were also elevated in serum, but no evidence of other infections or malignancies. Notably, the IgM level was higher in the CSF than in serum. Thus, cerebral toxoplasmosis was diagnosed. Soon after administration of oral sulfamethoxazole/trimethoprim and intravenous clindamycin in combination with short-term dexamethasone for the cerebral edema, her symptoms and signs began to improve. On day 229, both IgM and IgG titers in CSF had clearly decreased but remained essentially constant in serum. She was discharged without clinically significant neurological disorders. This case suggests that CSF specific anti-toxoplasma IgM titers might be useful for early diagnosis of cerebral toxoplasmosis after transplantation.

Topics: Antibodies, Protozoan; Biomarkers; Clindamycin; Cord Blood Stem Cell Transplantation; Early Diagnosis; Female; Graft vs Host Disease; Humans; Immunocompromised Host; Immunoglobulin M; Methylprednisolone; Middle Aged; Myelodysplastic Syndromes; Tacrolimus; Toxoplasma; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

A 31-year-old Malaysian man was presented with an episode of seizures by the roadside, after having been recently diagnosed as HIV positive accompanied with miliary tuberculosis. On physical examination, he was oriented to person, but not to time or place. There was no neck stiffness or papilloedema. The other systemic examination was unremarkable. Chest examination revealed crepitations at the upper zone of the right lung. After diagnosis suspicion, the case was confirmed as toxoplasma encephalitis by MRI and serological tests. Patient was treated with trimethoprim/sulfamethoxazole 480-2400 mg/day with folinic acid supplement for 60 days. Two months later, a repeat brain MRI showed resolution of the cerebral lesions.

Topics: Adult; AIDS Dementia Complex; Anti-Infective Agents; Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Male; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculoma, Intracranial

Cerebral toxoplasmosis is a rare but fatal complication in hematopoietic stem cell transplant patients, which mostly is caused by reactivation of latent disease.. In this study, we report an analysis of cerebral toxoplasmosis in a series of 170 allogeneic stem cell transplant patients during a 30-month period at our institution.. Among these allogeneic stem cell transplant patients, 5 were diagnosed with cerebral toxoplasmosis by brain magnetic resonance imaging and polymerase chain reaction of Toxoplasma gondii DNA. The incidence of cerebral toxoplasmosis was found to be 2.94%.. Mortality rate is known to be very high in cerebral toxoplasmosis; therefore, it is life saving to diagnose the disease in the early stages and start treatment promptly, especially in high-endemic countries like Turkey.

Topics: Adult; Anti-Bacterial Agents; Clindamycin; Coccidiostats; DNA, Protozoan; Female; Hematopoietic Stem Cell Transplantation; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Real-Time Polymerase Chain Reaction; Retrospective Studies; Toxoplasma; Toxoplasmosis, Cerebral; Transplantation, Homologous; Trimethoprim, Sulfamethoxazole Drug Combination

Toxoplasmosis is a well-recognized life-threatening complication of hematopoietic cell transplantation (HCT). This report describes a pediatric patient with stage 4 neuroblastoma who developed cerebral toxoplasmosis after tandem high-dose chemotherapy with autologous HCT. Toxoplasmosis is rare in patients undergoing autologous HCT; however, tandem autologous HCT is more immunosuppressive than a single autologous HCT. Toxoplasmosis is a potential complication in autologous as well as allogeneic transplants, and should be considered in any post-HCT patient with neurological dysfunction. Rapid diagnosis and immediate antimicrobial treatment are crucial to avoid morbidity and mortality. Evaluation of toxoplasma serology should be standard in all patients undergoing tandem autologous HCT and seropositive patients should be started on appropriate prophylactic therapy.

Topics: Child, Preschool; Hematopoietic Stem Cell Transplantation; Humans; Male; Neuroblastoma; Toxoplasmosis, Cerebral; Transplantation, Autologous; Trimethoprim, Sulfamethoxazole Drug Combination

Cotrimoxazole (trimethoprim/sulfamethoxazole [TMP-SMX]) is an alternative treatment for toxoplasmic encephalitis because it is inexpensive, well-tolerated, and as effective as pyrimethamine-sulfadiazine, which is the first-line drug regimen). We report results of a large cohort study of patients with acquired immunodeficiency syndrome who were treated for toxoplasmic encephalitis with cotrimoxazole. The mean follow-up period was more than three years. Our results confirm that cotrimoxazole is effective (85.5%), with a relatively low incidence of side effects (22%; 7.4% requiring treatment interruption). Relapse occurred in 30.1% of the patients at a mean +/- SD of 7.8 +/- 16.2 months after the first episode. The only risk factor for relapse was poor treatment and/or prophylaxis adherence. Mortality was significantly higher (P < 0.05) before 1996 than after 1996 (the era of highly active antiretroviral therapy). There was a non-significant trend towards a higher rate of relapse among patients treated before 1996 (P = 0.06). Consequently, cotrimoxazole could be a first-line drug regimen for curative treatment and prophylaxis of toxoplasmic encephalitis.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-HIV Agents; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; Cohort Studies; Female; Humans; Male; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Antiretroviral Therapy, Highly Active; Costs and Cost Analysis; Encephalitis; HIV Infections; Humans; Safety; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

A 36-year old female with acute myelogenous leukemia presented with a sudden decrease in vision one month following bone marrow transplantation (BMT). She had been taking multiple immunosuppressants to treat her recently-developed graft-versus-host-disease (GVHD). Visual acuity was 20/60 in her right eye and 20/25 in her left. Ophthalmic examination revealed mild inflammatory reaction in both the anterior chamber and the vitreous of both eyes, as well as densely opaque yellow-white infiltrates with well-demarcated borders in the posterior retina of both eyes. She was originally diagnosed as CMV retinitis, but treatment with ganciclovir failed to improve her ocular condition. Subsequent work-up, including serology and brain MRI, led to a diagnosis of combined ocular and cerebral toxoplasmosis. After 6 weeks of antiparasitic therapy, her retinal lesions became inactive and her cerebral lesions improved. Immunosuppressed patients with necrotizing retinochoroiditis should be suspected of having toxoplasmosis. Accurate differentiation between this condition and CMV, and early intervention with the appropriate treatment may be critical to preserve the best vision.

Topics: Adult; Anti-Bacterial Agents; Bone Marrow Transplantation; Chorioretinitis; Clindamycin; Cytomegalovirus Retinitis; Drug Therapy, Combination; Female; Functional Laterality; Humans; Leukemia, Myeloid, Acute; Magnetic Resonance Imaging; Tomography, Optical Coherence; Toxoplasmosis, Cerebral; Toxoplasmosis, Ocular; Transplantation, Homologous; Trimethoprim, Sulfamethoxazole Drug Combination

We describe a case of breakthrough cerebral toxoplasmosis during atovaquone therapy in a child who was intolerant of conventional prophylactic regimens after hematopoietic stem cell transplantation. The available data on the efficacy of atovaquone prophylaxis in Toxoplasma sero-positive stem cell transplant recipients remain limited, and other strategies, such as preemptive strategy using toxoplasma PCR or TMP-SMX desensitization should be considered in this setting.

Topics: Anti-Infective Agents; Atovaquone; Child; Encephalitis; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Time Factors; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

We conducted a retrospective study of AIDS-associated cerebral toxoplasmosis. Eighteen patients received pyrimethamine plus sulfadiazine and 25 co-trimoxazole, with comparable baseline characteristics. There were no differences in clinical outcomes, but co-trimoxazole was better tolerated (p = 0.066). There was also a trend towards more deaths among patients who received glucocorticoids.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiprotozoal Agents; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Kidney Diseases; Male; Pyrimethamine; Retrospective Studies; South Africa; Sulfadiazine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

We studied all human immunodeficiency virus (HIV)-infected patients with invasive pneumococcal disease who received their diagnosis during 1996-2002 to investigate the incidence of this disease in the highly active antiretroviral therapy era and to study the influence of CD4 lymphocyte count on the clinical presentation and outcome of disease. The overall incidence of invasive pneumococcal disease was 11.3 cases per 100,000 person-years in adult patients without known HIV infection and 677 cases per 100,000 person-years in HIV-infected patients. This incidence remained stable over the study period. Clinical presentation, severity of illness, and number of recurrent episodes were similar in patients with CD4+ cell counts of >200 or < or =200 cells/ microL. Patients receiving trimethoprim-sulfamethoxazole (TMP-SMZ) were more likely to present with TMP-SMZ-resistant pneumococci than were those who were not receiving this agent (76.7% vs. 43.6%; P=.007). The mortality rate was high (21%).

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Animals; Antiretroviral Therapy, Highly Active; Comorbidity; Drug Resistance, Multiple, Bacterial; Female; HIV; HIV Infections; Humans; Male; Microbial Sensitivity Tests; Pneumococcal Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Streptococcus pneumoniae; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim Resistance; Trimethoprim, Sulfamethoxazole Drug Combination

To reduce the number of daily pills for improving adherence to antiretrovirals, 17 protease inhibitor-treated patients receiving toxoplasmic encephalitis (TE) standard maintenance therapy were instead given cotrimoxazole 960 mg twice daily. After a median follow-up of 31 months, one relapsed after three months, TE relapse incidence = 2.1 cases per 100 patient-years (95% confidence interval, 0.05-11.3). This strategy could be useful for patients awaiting immune reconstitution which allows the interruption of TE maintenance therapy.

Topics: Animals; Anti-HIV Agents; Anti-Infective Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Female; Follow-Up Studies; HIV Infections; Humans; Male; Recurrence; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load

Highly active antiretroviral therapy (HAART) has resulted in a reduction of morbidity and mortality in HIV-associated cerebral opportunistic infection. Before HAART, up to 50% of all HIV-infected patients in Europe developed cerebral toxoplasmosis, an encephalitis caused by reactivation of Toxoplasma gondii infection. Although potent therapeutical options exist, the prognosis is still poor. We describe the course of 36 AIDS patients with cerebral toxoplasmosis and present a review of clinical signs, diagnosis, therapy, and survival times. The main criteria for differential diagnosis from other secondary neuromanifestations such as primary CNS lymphoma, progressive multifocal leukencephalopathy, abscesses, and ischemic infarctions are described. Indications and problems of stereotactic biopsy are discussed.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Brain; Dapsone; Diagnosis, Differential; Diagnostic Imaging; Drug Combinations; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pyrimethamine; Retrospective Studies; Sulfadoxine; Survival Rate; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

We here report a 32-year old homosexual man with AIDS who had an abnormal ACTH stimulation test while taking megestrol actetate (megace). On further evaluation, he was found to have recurrent Non-Hodgkin lymphoma (spleen) and intracranial toxoplasmosis, perhaps imitating or aggravating symptoms suggestive of adrenal insufficiency (AI). We diagnosed secondary AI due to megace treatment and tapered this medication under simultaneous hydrocortisone replacement therapy. After the patient's intracranial toxoplasmosis had been treated with intravenous bactrim, his symptoms disappeared. We conclude that patients with AIDS on megace therapy should receive special attention in regards to the potential development of AI, especially in stress situations such as infections or pain.

Topics: Acquired Immunodeficiency Syndrome; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Anti-Infective Agents; Diagnosis, Differential; Humans; Male; Megestrol Acetate; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

A case-control study to identify the risk factors for toxoplasmic encephalitis (TE) among HIV-infected patients with latent Toxoplasma gondii infection was performed in a teaching hospital in south-eastern Brazil. Although the subjects were all positive for serum IgG antibodies to Toxoplasma, some (the cases) developed TE during routine follow-up at the hospital whereas others (the controls) did not. Adjusted odds ratios (aOR) were estimated by multiple logistic regression after controlling for potential confounders. Only 46 (22%) of the 210 cases but 93 (45%) of the 205 controls were on prophylactic regimens with co-trimoxazole [aOR = 0.30; 95% confidence interval (CI) = 0.15-0.60]. Subjects with fewer than 100 (aOR = 37.09; CI =7.49-183.67) or between 100 and 200 CD4 cells/microl (aOR = 10.20; CI =2.00-51.90) were at substantially increased risk of developing TE than those with >400 CD4 cells/microl. Although the results of preliminary, unadjusted data analysis indicated that male sex and homosexual or bisexual activity might be additional risk factors, these associations were not found to be statistically significant by multiple regression analysis. In conclusion, no risk factors for TE other than low CD4 cell counts and failure to receive prophylaxis were found among HIV-infected Brazilian patients with past exposure to Toxoplasma. Seropositive patients with CD4 cell counts above 100/microl (the point at which specific prophylaxis is usually recommended) but below 200/microl might also benefit from effective anti-TE prophylaxis.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antibiotic Prophylaxis; Case-Control Studies; CD4 Lymphocyte Count; Encephalitis; Female; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Statistics as Topic; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

The spontaneous secretion in vitro of anti-Toxoplasma gondii antibodies by peripheral blood mononuclear cells was assessed in 69 patients with AIDS-related brain lesions. The sensitivity and specificity of this assay in the diagnosis of toxoplasmic encephalitis (TE) were found to be 85.4% and 92.8%, respectively. Twenty-four patients with TE were observed during 1-year follow-up after initiation of anti-Toxoplasma treatment and classified on the basis of their clinical and radiologic responses as sustained responders (SR; n = 11), incomplete responders (IR; n = 7) or transient responders (TR; n = 6). In vitro anti-T. gondii antibody secretion decreased as early as the first month after initiation of treatment and disappeared within the year in SRs, persisted in IRs, and decreased but rebounded at relapse in the TR patients. In vitro anti-T. gondii antibody, which reflects immune system activation by parasitic antigens, could be a surrogate marker of TE in AIDS patients.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Antibodies, Protozoan; Antiprotozoal Agents; Encephalitis; France; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Pyrimethamine; Retrospective Studies; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

To study the clinical course and outcome of toxoplasmic encephalitis (TE) in patients with acquired immunodeficiency syndrome (AIDS).. Patients infected with human immunodeficiency virus (HIV) and neurological abnormality compatible with diagnosis of TE were enrolled in the study. These patients were treated with combination of trimethoprim/sulfamethoxazole and pyrimethamine. Response to therapy was assessed by clinical examination and repeat CT/MRI scan done after three weeks of starting treatment. Those showing response were put on prophylactic therapy.. A total of 451 patients of HIV infections were admitted to this centre during the study period, of these 11 patients were diagnosed to have TE. The common presenting symptoms were fever (80%), seizures (45%), headache (45%) and altered sensorium (25%). Focal neurological deficit was present in 80% of cases. Nine cases had ring-enhancing lesions on CT scan while in the remaining two patient's ring lesions were seen on MRI. These were either multiple (55%) or solitary (45%). Antitoxoplasma antibody was detected in 10 patients. It was absent in one patient. Ten patients had clinical and radiological improvement with trimethoprim/sulfamethoxazole and pyrimethamine within 10 +/- 3 days of starting therapy. One patient died within 10 days of starting therapy.. Toxoplasmosis is a common opportunistic infection of the central nervous system in patients with AIDS. Majority of patients with cerebral toxoplasmosis present with focal neurological abnormality in presence of characteristic neuroradiological abnormality and positive antitoxoplasma antibody titer. Response to empirical therapy helps to confirm the diagnosis, lifelong prophylaxis there after prevents relapse of potentially fatal and easily treatable condition.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiprotozoal Agents; Drug Therapy, Combination; Female; Humans; Male; Pyrimethamine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Brain Neoplasms; Consciousness Disorders; Disease Susceptibility; Fatal Outcome; Hallucinations; Humans; Lymphoma, AIDS-Related; Male; Pneumonia, Pneumocystis; Psychoses, Substance-Induced; Sulfadiazine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

a retrospective study was designed to evaluate efficacy and tolerance of trimethoprim-sulphamethoxazole (TMP-SMZ) in AIDS patients with cerebral toxoplasmosis (TE).. we reviewed 471 patients with AIDS, and we analysed 71 AIDS patients with TE, who received intravenous therapy with TMP-SMZ (TMP: 10 mg/kg/day, SMZ: 50 mg/kg/day) for 4 weeks.. 35 patients (49.2%) had a complete regression of clinical signs, and a complete resolution of radiological lesions was noted in 41 patients (57.7%). Improvement of clinical signs and radiological lesions were observed in 27 patients (38%), and in nine patients (12.6%), respectively. In contrast, nine patients (12.6%) did not show any clinical change, or worsened. Twenty-two patients (30.9%) suffered from adverse cutaneous reactions, whereas many patients had haematological toxicity.. TMP-SMZ seems to be an efficient therapy for TE in AIDS patients, although further prospective, randomized therapeutic trials are required to confirm these results.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Female; Humans; Male; Retrospective Studies; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To describe the epidemiological characteristics of toxoplasmic encephalitis in HIV-infected patients with a more than 12-year follow-up.. From a data base of 1,628 AIDS subjects hospitalized from 1983 to 1994, we studied the epidemiological characteristics of 399 patients with toxoplasmic encephalitis. Diagnosis of toxoplasmic encephalitis was based on the association of central neurological disorders, typical lesions on CT scan or MRI, and favorable outcome under appropriate toxoplasmosis therapy.. Four hundred sixty-four cases of toxoplasmic encephalitis were reported in 399 patients (24.5% of the patients with AIDS). The overall incidence was 20.5 per 100 patients-year. Toxoplasmic encephalitis was the first AIDS defining event in 51% of the cases and revealed HIV infection in 13% of the cases. In the remaining 49%, the mean delay from AIDS diagnosis to toxoplasmic encephalitis was 13 months (range: 1-71 months). At the time of diagnosis, mean CD4 count was 44/mm3 (range: 0-408/mm3). Antibodies to Toxoplasma gondii were found in 97% of the cases. Before the first episode of toxoplasmic encephalitis, 58% of the patients were given antiretroviral therapy (mean: 17.8 months; range: 1-64 months). Of the 399 patients with toxoplasmic encephalitis, 366 (92%) did not receive any primary toxoplasmosis prophylaxis. Among them, 205 (56%) did not receive any drug prophylaxis, and 161 (44%) had Pneumocystis carinii pneumonia prophylaxis alone (aerosolized pentamidine). Thirty-three failures were observed (8%) with cotrimoxazole: 14 cases (3%) were considered to have irregular compliance. Sixty-five relapses were observed in 52 patients. At the end of the study 334 patients had died (84%). The median survival was 11.4 months (95% confidence interval, range: 10.4-12.4 months).. Toxoplasmic encephalitis incidence has decreased since the introduction of appropriate drug prophylaxis.

Topics: Adult; AIDS-Related Opportunistic Infections; Animals; Anti-Infective Agents; Antibodies, Protozoan; Antifungal Agents; Antiviral Agents; CD4 Lymphocyte Count; Chemoprevention; Coccidiostats; Databases as Topic; Female; Follow-Up Studies; France; HIV Infections; Humans; Incidence; Magnetic Resonance Imaging; Male; Pentamidine; Pneumonia, Pneumocystis; Recurrence; Survival Rate; Time Factors; Tomography, X-Ray Computed; Toxoplasma; Toxoplasmosis, Cerebral; Treatment Failure; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Our objective was to examine the accuracy of diagnosis of HIV-associated central nervous system (CNS) toxoplasmosis. Individuals diagnosed with HIV-associated CNS toxoplasmosis and controls were ascertained from a population-based database. Diagnosis was confirmed by response to therapy or by histology. Symptoms, results of anti-Toxoplasma serology and use of Pneumocystis carinii pneumonia (PCP) prophylaxis were recorded. Central nervous system toxoplasmosis was confirmed in 54 (76%) of 75 patients. Reactive anti-Toxoplasma serology was associated with CNS toxoplasmosis (OR=20.4, 95% CI 3.1-175.8). Adjusting for CD4 and use of dapsone or aerosolized pentamidine, trimethoprim-sulphamethoxazole (TMP-SMX) for PCP prophylaxis was associated with lower likelihood of CNS toxoplasmosis (OR 0.3, 95% CI 0.1-0.7). Diagnosis of CNS toxoplasmosis is often incorrect. Another diagnosis is most likely in patients who are anti-Toxoplasma seronegative or who are receiving prophylactic TMP-SMX.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; False Positive Reactions; Humans; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Besides Pneumocystis carinii bacterial pathogens represent the most common aetiology of pulmonary infections in HIV-positive patients. However, the impact of PCP prophylaxis on the incidence of bacterial pneumonia in HIV-positive patients using pentamidine or co-trimoxazole is still unknown.. We analysed retrospectively the data of 80 consecutive HIV-positive patients with a CD4-cell count < 300/microliter. The total observation period was 1993 patient months. Type and duration of chemoprophylaxis, frequency of bacterial pneumonia, PCP, extrapulmonary bacterial infections and cerebral toxoplasmosis were documented in a standardised manner. For statistical analysis we used the Kaplan-Meier test for the time to a recurrence of the various infections under both prophylaxis regimens and the Odds ratio for determination of the relative risk.. We followed up 47 patients inhaling 300 mg pentamidine monthly for a total of 1133 months and 33 patients taking 480 mg co-trimoxazole per day p.o. for a total of 860 months. There were no statistically significant differences between the two groups in respect of demographic parameters, stage and therapy of HIV infection and distribution of risk groups. We found seven bacterial pneumonias in the co-trimoxazole group and 13 in the pentamidine group (not significant); the most common causative organisms were S. pneumoniae (n = 4), S. aureus (n = 3) and H. influenzae (n = 3). Furthermore, in the pentamidine group 12 PCP and nine cases of toxoplasma encephalitis were observed, whereas none of these infections occurred in the co-trimoxazole group (p < 0.05). Two of the patients taking co-trimoxazole and 15 of those inhaling pentamidine had extrapulmonary bacterial infections (p < 0.05), the most frequently identified pathogen being S. aureus (n = 7). The two prophylaxis groups did not differ significantly with regard to laboratory data, course and therapy of the bacterial pneumonias.. There was no significant influence of chemoprophylaxis on the incidence of bacterial pneumonia in patients with advanced HIV-disease in our study. Since S. pneumoniae represents the most common causative agent, we suggest immunisation with a polyvalent pneumococcal vaccine at an early stage of HIV-infection.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; CD4 Lymphocyte Count; Female; Humans; Male; Middle Aged; Odds Ratio; Pentamidine; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Retrospective Studies; Risk; Toxoplasmosis, Cerebral; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Using results of a multicentric randomized prospective trial of primary prophylaxis of Pneumocystis carinii pneumonia in HIV-infected patients which compared sulfamethoxazole-trimethoprim and pentamidine isethionate, the risk to develop cerebral toxoplasmosis was analyzed in the two assigned groups and in the groups of patients who stopped sulfamethoxazole-trimethoprim prophylaxis. The risk to develop cerebral toxoplasmosis appeared significantly higher in the group of patients who stopped sulfamethoxazole-trimethoprim consecutively to cutaneous hypersensitivity.

Topics: AIDS-Related Opportunistic Infections; Drug Eruptions; Drug Therapy, Combination; Follow-Up Studies; Humans; Multicenter Studies as Topic; Pentamidine; Pneumonia, Pneumocystis; Probability; Prospective Studies; Randomized Controlled Trials as Topic; Risk; Survival Rate; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

In a case-control study, prophylaxis with cotrimoxazole for toxoplasmic encephalitis (TE) in HIV-infected patients was evaluated. Cotrimoxazole had been given as PCP prophylaxis. 20 patients with TE were identified and 72 matching control cases were found. All patients had IgG-antibodies to Toxoplasma gondii and CD4+ T-cell counts < or = 100/microliter. The use and duration of cotrimoxazole prophylaxis were recorded. It was found that among the patients with TE, none had used cotrimoxazole for > 70% of the observation time, and that the 1-y incidence was 0% in the control group vs. 41% in those patients without sufficient cotrimoxazole use. The conclusion is that cotrimoxazole is effective as primary prophylaxis for TE, even in a dose of 480 mg daily.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Case-Control Studies; Female; HIV Infections; Humans; Male; Middle Aged; Retrospective Studies; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Dapsone; Drug Therapy, Combination; Humans; Pneumonia, Pneumocystis; Pyrimethamine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the incidence of and risk factors for toxoplasmic encephalitis among HIV-infected persons.. Medical facility-based prospective medical record reviews of consecutive patients.. We analysed data collected from January 1990 through August 1995 in more than 90 inpatient and outpatient medical facilities in nine US cities. Incidence was calculated as cases per 100 person-years and risk ratios (RR) for annual incidence were calculated using proportional hazards regression while controlling for city, sex, race, age, county of birth, HIV exposure mode, and prior prescription of trimethoprim-sulfamethoxazole (TMP-SMX).. The incidence of TE was 4.0 cases per 100 person-years among persons with a CD4+ T-lymphocyte count of < 100 x 10(6)/l. In multivariate analysis, among the nine cities the annual incidence of toxoplasmosis was significantly lower only in Denver [RR, 0.3; 95% confidence interval (CI), 0.1-0.7; referent city, Seattle]. Persons prescribed TMP-SMX were half as likely to develop toxoplasmic encephalitis as those who were not (RR, 0.5; 95% CI, 0.4-0.7). Of the 4173 persons with AIDS (1987 Centers for Disease Control and Prevention definition) who died during the study period, 267 (6.4%) had toxoplasmic encephalitis in the course of HIV disease.. Toxoplasmic encephalitis in HIV-infected persons varies by geographic area in the United States. TMP-SMX reduces the risk for toxoplasmic encephalitis.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; CD4 Lymphocyte Count; Female; HIV-1; Humans; Male; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

In France, where 70% of adults are latently infected by toxoplasma, from 20% to 40% of patients with AIDS developed toxoplasmic encephalitis until recently. The prophylactic use of drugs which are active against pneumocystis and toxoplasma has proven to be efficient. These drugs are trimethoprim-sulfamethoxazole or dapsone-pyrimethamine. With the extent of these primary prophylaxis, there is a decrease of risk of toxoplasma encephalitis; thus the rate of toxoplasma encephalitis among opportunistic infections has fallen off from 19% of the patients in 1988 to 6% in 1994, in the department of infectious diseases of the Pitié-Salpêtrière hospital. However, toxoplasmic abscesses occurring despite the prophylaxis are frequently slow growing lesions which can become huge with a moderate mass effect, mimicking the pattern of primary cerebral lymphoma. The rule of antitoxoplasmic trial treatment must be strictly followed, even under prophylaxis.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antiprotozoal Agents; Brain Abscess; Brain Neoplasms; Chemoprevention; Dapsone; Diagnosis, Differential; Drug Combinations; Encephalitis; France; Humans; Lymphoma, AIDS-Related; Pyrimethamine; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Humans; Male; Middle Aged; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Encephalitis; Female; Humans; Male; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; AIDS-Related Opportunistic Infections; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Retrospective Studies; Sulfonamides; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Humans; Injections, Intravenous; Male; Middle Aged; Recurrence; Tomography, X-Ray Computed; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

To study Toxoplasma encephalitis (TE) in advanced HIV infection, including predictive factors, possible prophylactic regimens and impact on survival.. Epidemiological analysis of data collected prospectively during the Alpha study, a double-blind, randomized clinical trial, comparing two doses of dideoxyinosine in patients with advanced HIV disease.. First episode of TE occurred in 75 out of 499 patients participating in the trial.. Kaplan-Meier estimates and semi-parametric Cox's model were used.. A low CD4 cell count and a positive Toxoplasma serology were strongly predictive of the occurrence of TE. In patients with CD4 counts < 100 x 10(6)/l and a positive Toxoplasma serology at entry to the study, the 12-month TE incidence was 25.4%. Patients who were receiving at entry any of the following potentially antitoxoplasmic drugs: trimethoprim-sulphamethoxazole, pyrimethamine, dapsone, pyrimethamine-sulphadoxine or sulphadiazine, had a lower TE incidence than those who were not; 6.2 versus 18.8%, respectively (P < 0.001). The rate of survival 12 months after TE was 29.6%. Even after adjusting the major prognostic covariates, TE was predictive of death (P < 0.001; relative risk, 1.8).. The high HIV incidence, morbidity and mortality in high-prevalence areas suggests that primary prophylaxis should be given in patients at high risk for toxoplasmic reactivation.

Topics: Adult; AIDS-Related Opportunistic Infections; Dapsone; Encephalitis; Female; Humans; Male; Middle Aged; Pyrimethamine; Sulfadiazine; Sulfadoxine; Survival Rate; Toxoplasmosis; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the efficacy of low-dose trimethoprim-sulfamethoxazole (trimethoprim, 160 mg plus sulfamethoxazole, 800 mg; one tablet twice daily, 2 days per week) as primary prophylaxis against toxoplasmic encephalitis in patients with human immunodeficiency virus (HIV) infection and previous Pneumocystis carinii pneumonia.. A retrospective study.. Tertiary referral teaching hospital.. During a 3-year period after primary episodes of P. carinii pneumonia, 60 patients received trimethoprim-sulfamethoxazole, and 95 patients received pentamidine (aerosolized in 78 patients and intravenous in 17 patients) as secondary prophylaxis.. No patient in the trimethoprim-sulfamethoxazole group and no patient seronegative for Toxoplasma gondii developed toxoplasmic encephalitis, compared with 12 of 36 (33%; 95% Cl, 19% to 51%) seropositive patients in the pentamidine group (trimethoprim-sulfamethoxazole compared with pentamidine, P = 0.008). A significant difference was seen in the time to development of toxoplasmic encephalitis between the trimethoprim-sulfamethoxazole group (no case at 1153 days) and the pentamidine group (median time, 460 days) (P = 0.004). Neither the CD4+ lymphocyte count at the start of prophylaxis nor zidovudine therapy during the period of prophylaxis influenced the rate of toxoplasmic encephalitis in any group.. Low-dose trimethoprim-sulfamethoxazole (four tablets per week) appears to be effective prophylaxis against toxoplasmic encephalitis in HIV-infected patients with previous P. carinii pneumonia. A prospective, randomized, controlled study is needed to further evaluate these findings.

Topics: Acquired Immunodeficiency Syndrome; Animals; Antibodies, Protozoan; CD4-Positive T-Lymphocytes; Encephalitis; Follow-Up Studies; Humans; Immunoglobulin G; Leukocyte Count; Male; Pentamidine; Pneumonia, Pneumocystis; Retrospective Studies; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine