RESUMO
BACKGROUND: Despite recent advances for treating cerebral toxoplasmosis (CT), monitoring the parasite burden and treatment response is still challenging. miRNAs are small non-coding RNAs with regulatory functions that can be used in diagnosis and treatment monitoring. We investigated the changes in miR-146a, BAG-1 gene, IL-6, and IL-10 tissue levels in the brain of BALB/c mice with chronic CT caused by the PRU strain of T. gondii following anti-parasitic and antibiotic treatment. METHOD: Fifty-three 6-to 8-week-old BALB/c mice were infected using intraperitoneal inoculation of cerebral cysts of T. gondii PRU strain and then divided into five groups as follows: group 1 included mice treated with 100 mg/kg/d Atovaquone (AT), group 2 included mice treated with 400 mg/kg/d clindamycin (CL), group 3 included mice treated with combination therapy (AT + CL), group 4 included infected untreated mice as a positive control (PC), and; group 5 included uninfected untreated mice as negative control (NC). After the completion of the treatment course, tissue level of mir-146a, miR-155, BAG-1 gene, IL-6, and IL-10 was investigated with real-time polymerase chain reaction. The IL-6/IL-10 ratio was calculated as an indicator of immune response. Moreover, brain cyst numbers were counted on autopsy samples. RESULTS: miR-146a, IL-6, IL-10, and BAG-1 genes were expressed in PC, but not in the NC group; miR-146a, IL-6, IL-10, and BAG-1 gene expression were significantly lower in AT, CL, and AT + CL compared with PC. MiR-146a and BAG-1 levels in AT and CL were not different statistically, however, they both had lower levels compared to AT + CL (P < 0.01). There was no difference in the expression of IL-6 and IL-10 between treatment groups. BAG-1 expression was significantly lower in AT, than in CL and AT + CL (P < 0.0089 and < 0.002, respectively). The PC group showed a higher ratio of IL-6/IL-10, although this increase was not statistically significant. It is noteworthy that the treatment with AT reduced this ratio; in the inter-group comparison, this ratio showed a decrease in the AT and AT + CL compared to the PC. The number of brain tissue cysts was significantly lower in AT, CL, and AT + CL, than in PC (p < 0.0001). AT had significantly lower brain cysts than CL and AT + CL (P < 0.0001). CONCLUSION: It seems that the factors studied in the current research (microRNA and cytokines) are a suitable index for evaluating the response to antiparasitic and antibiotic treatment. However, more studies should be conducted in the future to confirm our findings.
Assuntos
Cistos , MicroRNAs , Toxoplasma , Toxoplasmose Cerebral , Animais , Camundongos , Toxoplasmose Cerebral/tratamento farmacológico , Atovaquona/farmacologia , Atovaquona/uso terapêutico , Citocinas/metabolismo , Clindamicina/farmacologia , Clindamicina/uso terapêutico , Interleucina-10/genética , Interleucina-6 , Toxoplasma/metabolismo , MicroRNAs/genética , AntibacterianosRESUMO
BACKGROUND: Although the price increase of pyrimethamine in 2015 received heavy media coverage, there are little data regarding specific implications to hospitals and the total costs of treating inpatients with toxoplasmosis encephalitis (TE). METHODS: Using average drug wholesale costs, we estimated the inpatient drug costs of TE drugs 3 years prepyrimethamine and postpyrimethamine price increase in August 2015. The drug regimens and total doses were determined through retrospective chart review of patients living with HIV who received treatment for TE while inpatient during this period. RESULTS: The 3-year pre-increase TE drug costs for 66 admissions were estimated at $50,310 compared with a total drug cost of $1,026,006 for 61 admissions postincrease. Pyrimethamine made up 98% of the drug costs postincrease, compared with 57% pre-increase. Pyrimethamine-based regimens were the most frequently used throughout the study period. CONCLUSIONS: The price increase of pyrimethamine in 2015 led to a substantial and unnecessary financial burden to hospitals. This required health care systems to shift valuable resources to continue to provide medications to a vulnerable patient population. There has been more focus on providing high-value care in recent years. Our study highlights the need for further examination of pharmaceutical companies' arbitrary determination of medication costs and how they contribute to patient care.
Assuntos
Encefalite , Infecções por HIV , Toxoplasmose Cerebral , Estresse Financeiro , Infecções por HIV/tratamento farmacológico , Humanos , Preparações Farmacêuticas , Pirimetamina/uso terapêutico , Estudos Retrospectivos , Provedores de Redes de Segurança , Toxoplasmose Cerebral/induzido quimicamente , Toxoplasmose Cerebral/tratamento farmacológicoRESUMO
Cerebral toxoplasmosis is caused by the protozoan Toxoplasma gondii because of reactivation of latent tissue cysts in the Acquired Immunodeficiency Syndrome (AIDS) patients with severe immunosuppression. The objective of this study was to evaluate the benefit of co-trimoxazole in presumptive and prevention of cerebral toxoplasmosis in Human Immunodeficiency Virus (HIV)/AIDS patients at Bobo-Dioulasso Hospital in Burkina Faso from June 2012 to October 2014. ELISA and ELFA were performed on serum for the quantitative determination of IgG and IgM anti-T. gondii, respectively. The seroprevalence of toxoplasmosis was 29.3%. No IgM antibodies for T. gondii were found. Six patients with Toxoplasma-specific antibodies presented cerebral toxoplasmosis. All patients were infected by HIV-1 with the median of CD4+ T lymphocytes at 141 cells/µl. No patient was under antiretroviral therapy. No case of cerebral toxoplasmosis was noted in patients receiving co-trimoxazole in prevention. Presumptive treatment of cerebral toxoplasmosis with co-trimoxazole was effective in all patients with a significant clinical improvement in 83.3%. These results attest the benefit of cotrimoxazole in cerebral toxoplasmosis treatment in countries where drug resources are limited when sulfadiazine is not available. Ours finding highlight the importance of establishing toxoplasmosis chemoprophylaxis to HIV with severe immunosuppression patients and positive Toxoplasma serology.
Assuntos
Infecções por HIV/complicações , Toxoplasmose Cerebral/complicações , Toxoplasmose Cerebral/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Adulto , Antibacterianos/economia , Antibacterianos/uso terapêutico , Burkina Faso/epidemiologia , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Toxoplasmose Cerebral/sangue , Toxoplasmose Cerebral/epidemiologia , Combinação Trimetoprima e Sulfametoxazol/economia , Adulto JovemAssuntos
Encéfalo/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Toxoplasma/isolamento & purificação , Toxoplasmose Cerebral/líquido cefalorraquidiano , Toxoplasmose Cerebral/patologia , Condicionamento Pré-Transplante/efeitos adversos , Adulto , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Biópsia , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Ciclofosfamida/uso terapêutico , Febre/etiologia , Cefaleia/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Agonistas Mieloablativos/uso terapêutico , Reação em Cadeia da Polimerase , Toxoplasmose Cerebral/tratamento farmacológico , Toxoplasmose Cerebral/microbiologia , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Vômito/etiologiaAssuntos
Pesquisa Biomédica , Doenças Transmitidas por Alimentos/parasitologia , Toxoplasmose/parasitologia , Animais , Pesquisa Biomédica/economia , Parasitologia de Alimentos , Doenças Transmitidas por Alimentos/psicologia , Doenças Transmitidas por Alimentos/terapia , Interações Hospedeiro-Parasita , Humanos , Lisossomos/fisiologia , Toxoplasma/fisiologia , Toxoplasmose/psicologia , Toxoplasmose/terapia , Toxoplasmose Cerebral/parasitologia , Toxoplasmose Cerebral/psicologia , Toxoplasmose Cerebral/terapiaRESUMO
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.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Anti-Infecciosos/administração & dosagem , Clindamicina/administração & dosagem , Pirimetamina/administração & dosagem , Sulfadiazina/administração & dosagem , Toxoplasmose Cerebral/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Adulto , Idoso , Anti-Infecciosos/uso terapêutico , Clindamicina/uso terapêutico , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Pobreza , Pirimetamina/uso terapêutico , Estudos Retrospectivos , Sulfadiazina/uso terapêutico , Toxoplasmose Cerebral/diagnóstico , Toxoplasmose Cerebral/mortalidade , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoAssuntos
Humanos , Toxoplasmose/classificação , Toxoplasmose/complicações , Toxoplasmose/diagnóstico , Toxoplasmose/tratamento farmacológico , Toxoplasmose/epidemiologia , Toxoplasmose/terapia , Toxoplasmose Congênita/diagnóstico , Toxoplasmose Congênita/prevenção & controle , Toxoplasmose Congênita/terapia , Toxoplasmose Congênita/transmissão , Toxoplasma , Síndrome da Imunodeficiência Adquirida/complicações , Toxoplasmose Cerebral/diagnóstico , Toxoplasmose Cerebral/prevenção & controle , Toxoplasmose Cerebral/terapia , Toxoplasmose Ocular/complicações , Toxoplasmose Ocular/diagnóstico , Toxoplasmose Ocular/epidemiologia , Toxoplasmose Ocular/terapia , Toxoplasmose Ocular/transmissãoAssuntos
Toxoplasmose Cerebral/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Anti-Infecciosos/economia , Anti-Infecciosos/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Custos e Análise de Custo , Encefalite/tratamento farmacológico , Encefalite/microbiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Segurança , Toxoplasmose Cerebral/complicações , Combinação Trimetoprima e Sulfametoxazol/economiaRESUMO
OBJECTIVE: To estimate incidence rates of opportunistic diseases (ODs) and mortality for patients with and without a history of OD among HIV-infected patients in Côte d'Ivoire. METHODS: Using incidence density analysis, we estimated rates of ODs and chronic mortality by CD4 count in patients in a cotrimoxazole prophylaxis trial in Abidjan before the highly active antiretroviral therapy (HAART) era. Chronic mortality was defined as death without a history of OD or death more than 30 days after an OD diagnosis. We used Poisson's regression to examine the effect of OD history on chronic mortality after adjusting for age, gender, and current CD4 count. RESULTS: Two hundred and seventy patients (40% male, mean age 33 years, median baseline CD4 count 261 cells/microl) were followed up for a median of 9.5 months. Bacterial infections and tuberculosis were the most common severe ODs. Of 47 patients who died, 9 (19%) died within 30 days of an OD, 26 (55%) died more than 30 days after an OD, and 12 (26%) died with no OD history. The chronic mortality rate was 31.0/100 person-years for those with an OD history, and 11.1/100 person-years for those with no OD history (rate ratio (RR) 2.81, 95% confidence interval (CI): 1.43 - 5.54). Multivariate analysis revealed that OD history remained an independent predictor of mortality (RR 2.15, 95% CI: 1.07 - 4.33) after adjusting for CD4 count, age and gender. CONCLUSIONS: Before the HAART era, a history of OD was associated with increased chronic HIV mortality in Côte d'Ivoire, even after adjusting for CD4 count. These results provide further evidence supporting OD prophylaxis in HIV-infected patients.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Causas de Morte , Infecções por HIV/mortalidade , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/parasitologia , Adulto , Distribuição por Idade , Infecções Bacterianas/mortalidade , Contagem de Linfócito CD4 , Doença Crônica , Efeitos Psicossociais da Doença , Côte d'Ivoire/epidemiologia , Feminino , Seguimentos , Infecções por HIV/imunologia , Humanos , Incidência , Malária/mortalidade , Masculino , Análise Multivariada , Infecções por Mycobacterium/mortalidade , Micoses/mortalidade , Vigilância da População , Análise de Regressão , Fatores de Risco , Distribuição por Sexo , Toxoplasmose Cerebral/mortalidade , Tuberculose/mortalidadeRESUMO
BACKGROUND: 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. OBJECTIVES: 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. SEARCH STRATEGY: A comprehensive search of relevant databases and other sources was conducted to identify relevant studies. SELECTION CRITERIA: Randomised double-blinded trials were included. DATA COLLECTION AND ANALYSIS: Data were extracted using standardised forms and analysed using Rev Man 4.2.7 software. MAIN RESULTS: 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). AUTHORS' CONCLUSIONS: 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.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Anti-Infecciosos/uso terapêutico , Meningoencefalite/tratamento farmacológico , Toxoplasmose Cerebral/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/parasitologia , Adulto , Terapia Antirretroviral de Alta Atividade , Clindamicina/uso terapêutico , Humanos , Meningoencefalite/parasitologia , Pobreza , Pirimetamina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoRESUMO
OBJECTIVES: This retrospective study was carried out to determine the prevalence of cerebromeningeal diseases at the Fann Teaching Hospital Infectious Diseases Clinic, in Dakar, and to describe their epidemiological, clinical, and etiological features. PATIENTS AND METHODS: Data was collected for analysis from patients files recorded from January 1, 2001 to December 31, 2003. RESULTS: Four hundred seventy cases were identified (11.4% of total admissions) with a M/F sex ratio of 1.38 and a mean age of 33 years. Eighty-nine patients were infected by HIV and clinical presentations included fever (78%), meningeal syndrome (57.4%), coma (64.9%), convulsions (19%), focal neurological deficits (15.5%), and cranial nerves dysfunction (7.2%). Etiologies presented as cerebral malaria (85 cases), purulent meningitis (51 cases), neuromeningeal cryptococcosis (37 cases), tuberculous meningitis (11 cases), intracranial abscess (10 cases), toxoplasma encephalitis (4 cases), cerebrovascular attack (11 cases), and cerebromeningeal hemorrhages (3 cases). In as many as 248 cases (52.8%) no etiology could be found. The case fatality rate was 44.5% overall (209 deaths) and 68.5% among HIV-infected patients. Neurological sequels were found in 22 survivors (8.8%), consisting in focal neurological deficit (12 cases), deafness (5 cases), diplopia (2 cases), dementia (2 cases), postmeningitic encephalitis (1 case). CONCLUSION: These results show the need to improve our technical capacities in our diagnostic laboratories, the prevention of opportunistic infections in the course of HIV/AIDS infection, and the involvement of various specialists in the management of cerebromeningeal diseases.
Assuntos
Encefalopatias/epidemiologia , Meningite/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/epidemiologia , Criança , Pré-Escolar , Coma/epidemiologia , Grupos Diagnósticos Relacionados , Encefalite/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Mortalidade Hospitalar , Hospitais Universitários/estatística & dados numéricos , Humanos , Malária Cerebral/epidemiologia , Masculino , Meningite Criptocócica/epidemiologia , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Estações do Ano , Senegal/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Toxoplasmose Cerebral/epidemiologia , Tuberculose do Sistema Nervoso Central/epidemiologiaRESUMO
O diagnóstico da neurotoxoplasmose em pacientes com síndrome da imunodeficiência adquirida baseia-se fundamentalmente nos achados tomográficos ou de ressonância magnética e na resposta ao tratamento específico. Estudamos 55 pacientes com SIDA e neurotoxoplasmose, de acordo com estes critérios diagnósticos (grupo 1); 37 pacientes com SIDA e comprometimento neurológico por outra etiologia (grupo 2) e 16 indivíduos anti-HIV negativo, com outras doenças neurológicas (grupo 3), pesquisando IgG, anti-T. gondii, no soro e no líquor, utilizando a reação de imunofluorescência indireta. Em 72 casos, determinamos os teores totais destes anticorpos aí presentes, com objetivo de avaliar a produção local, no sistema nervoso central, de anticorpos específicos e correlacionar os títulos com atividade da infecção, em pacientes com SIDA e neurotoxoplasmose. Evidência de produção local destes anticorpos foi detectada em 42,8% dos pacientes do grupo 1, em 29,1% dos pacientes do grupo 2 e em nenhum paciente do grupo 3. O teste apresentou especificidade intermediária (70,8%), porém não foi útil para o diagnóstico diferencial da neurotoxoplasmose em pacientes com SIDA, em nosso estudo. Por outro lado, títulos de IgG no líquor > 1/64 alcançaram 100% de especificidade para o diagnóstico de neurotoxoplasmose na SIDA.
Assuntos
Humanos , Animais , Infecções Oportunistas Relacionadas com a AIDS , Anticorpos Antiprotozoários , Imunoglobulina G , Toxoplasma , Toxoplasmose Cerebral , Técnica Indireta de Fluorescência para Anticorpo , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
The diagnosis of neurotoxoplasmosis in patients with acquired immunodeficiency syndrome is mainly based on tomographic or magnetic resonance findings and on the response to specific treatment. We studied 55 patients with AIDS and neurotoxoplasmosis according to these diagnostic criteria (group 1), 37 patients with AIDS and neurological involvement of other etiology (group 2), and 16 anti-HIV-negative individuals with neurological manifestations (group 3). Serum and cerebrospinal fluid were examined for the presence of anti-T. gondii IgG, by indirect immunofluorescence. In 72 of them, the total amounts of these antibodies were determined in order to assess local production of anti-T. gondii antibodies in the central nervous system and to correlate their titers with infection activity in patients with AIDS and neurotoxoplasmosis. IgG titers > or = 1/64 in cerebrospinal fluid reached 100% specificity for the diagnosis of neurotoxoplasmosis in AIDS. Evidence of local synthesis of these antibodies was detected in 42.8% of patients of group 1, in 29.1% of patients of group 2 and in no patient of group 3. The test showed 70.8% specificity and therefore was not useful in our study for the differential diagnosis of neurotoxoplasmosis in patients with AIDS.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Anticorpos Antiprotozoários/biossíntese , Imunoglobulina G/biossíntese , Toxoplasma/imunologia , Toxoplasmose Cerebral/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Animais , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/líquido cefalorraquidiano , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Toxoplasmose Cerebral/imunologiaRESUMO
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.
Assuntos
Transplante de Células-Tronco de Sangue Periférico , Reação em Cadeia da Polimerase/métodos , Toxoplasmose/diagnóstico , Animais , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Antiprotozoários/uso terapêutico , Sistemas Computacionais , DNA de Protozoário/análise , Previsões , Humanos , Hospedeiro Imunocomprometido , Programas de Rastreamento/economia , Pré-Medicação , Sensibilidade e Especificidade , Estudos Soroepidemiológicos , Toxoplasma/genética , Toxoplasma/imunologia , Toxoplasmose/economia , Toxoplasmose/epidemiologia , Toxoplasmose/prevenção & controle , Toxoplasmose Cerebral/diagnóstico , Toxoplasmose Cerebral/epidemiologia , Toxoplasmose Cerebral/prevenção & controle , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoRESUMO
Although acquired immunodeficiency syndrome (AIDS) is not directly fatal, individuals with the disease are susceptible to a host of life-threatening opportunistic infections and complications. This article focuses on the central nervous system (CNS) complications of HIV/AIDS and computed tomography's role in diagnosing these conditions. After completing the article, readers will know the signs and symptoms, causes or proposed causes and computed tomographic (CT) appearance of 4 important CNS complications of HIV/AIDS: Progressive multifocal leukoencephalopathy (PML). Toxoplasmosis. CNS lymphoma. AIDS dementia complex (ADC).
Assuntos
Complexo AIDS Demência/diagnóstico por imagem , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico por imagem , Leucoencefalopatia Multifocal Progressiva/diagnóstico por imagem , Linfoma Relacionado a AIDS/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Toxoplasmose Cerebral/diagnóstico por imagem , Síndrome da Imunodeficiência Adquirida/diagnóstico , Encéfalo/diagnóstico por imagem , Feminino , Humanos , MasculinoRESUMO
PURPOSE: We investigated the role of Magnetic Resonance Imaging (MRI) in the diagnosis of neurotoxoplasmosis and in the evaluation of drug treatment response. MATERIAL AND METHODS: Twenty-six AIDS patients (22 men and 4 women, mean age 26.7 years) with clinical suspicion of neurotoxoplasmosis were examined. A patient was considered to have neurotoxoplasmosis if there were signs of focal neurologic impairment and a positive/questionable response to the serum test for Toxoplasma gondii. MR images were acquired with T1-weighted spin-echo (SE) and inversion recovery (IR) sequences and with T2-weighted SE sequences. Gd-DTPA was administered in all cases. After the beginning of therapy with sulfadiazine and pyrimethamine all patients were submitted to clinical and neuroradiologic follow-up for 60 days. RESULTS: MR examinations on admission demonstrated at least one brain lesion in all patients and multifocal involvement in 70% of cases. Enhancing lesions were found in 90% of patients (83% ring enhancement, 4% focal enhancement, 3% mixed patterns). The most frequent lesion sites were the basal ganglia and thalami (70%). The brain lesions were subdivided into 4 groups by their morphology and signal patterns. DISCUSSION: The time course of clinical and neuroradiologic responses demonstrates a rapid improvement after the first week of therapy, which stabilized after the second week. Pearson correlation between clinical and neuroradiologic treatment responses showed a nearly linear correlation (r = .97; p < .001). The diagnosis was then confirmed in all patients based on the positive response to the serum test for Toxoplasma gondii (IgG > 12 UI/mL) and/or clinical and neuroradiologic improvement after therapy. DISCUSSION AND CONCLUSIONS: This study demonstrates the accuracy of MRI in the detection of toxoplasmosis brain lesions and in the evaluation of treatment response.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/patologia , Antiprotozoários/uso terapêutico , Imageamento por Ressonância Magnética , Pirimetamina/uso terapêutico , Sulfadiazina/uso terapêutico , Toxoplasmose Cerebral/tratamento farmacológico , Toxoplasmose Cerebral/patologia , Adulto , Feminino , Humanos , Masculino , Reprodutibilidade dos TestesRESUMO
Neurological complications occur in 40% of "human immunodeficiency virus type 1" (HIV-1)-infected patients. Aim of the study was to evaluate the diagnostic yield of stereotactic brain biopsy and non invasive diagnostic procedures (CT, antitoxoplasma antibodies) and to calculate the benefit of the brain biopsy for the patient and the costs of both methods. From October 1989 through September 1995 we biopsied 44 of 2749 (2%) HIV-1-infected patients after non invasive diagnostic procedures had been performed. In 93% of the patients an unambiguous diagnosis was possible based on the biopsy and lead in 73% of the patients to a change of therapy. No complications occurred after biopsy. 40 CTs and 15 MRIs were done. The radiological appearance of toxoplasmosis and non Hodgkin lymphoma (NHL) differed from that of progressive multifocal leucencephalopathy (PML) in respect to enhancement (PML). CT showed a sensitivity of 55% (toxoplasmosis, NHL) and 78% (PML) and a specificity of 83% (PML), 84% (NHL) and 96% (toxoplasmosis), respectively. Antitoxoplasma antibodies showed a sensitivity of 45%, only. The stereotactic brain biopsy was more expensive (20.166,- ATS) than CT, MRI and antitoxoplasma antibodies (4109,- ATS up to 6959,- ATS). We conclude that stereotactic brain biopsy is an efficient and safe and for the patients important diagnostic procedure. In selected patients even expensive investigations should be undertaken considering specific therapy and cost effective homecare.
Assuntos
Complexo AIDS Demência/patologia , Infecções Oportunistas Relacionadas com a AIDS/patologia , Biópsia/economia , Encefalopatias/patologia , Técnicas Estereotáxicas/economia , Complexo AIDS Demência/economia , Infecções Oportunistas Relacionadas com a AIDS/economia , Adulto , Encefalopatias/economia , Neoplasias Encefálicas/economia , Neoplasias Encefálicas/patologia , Análise Custo-Benefício , Feminino , Humanos , Leucoencefalopatia Multifocal Progressiva/economia , Leucoencefalopatia Multifocal Progressiva/patologia , Linfoma Relacionado a AIDS/economia , Linfoma Relacionado a AIDS/patologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Testes Sorológicos/economia , Toxoplasmose Cerebral/economia , Toxoplasmose Cerebral/patologiaRESUMO
Unlike traditional approaches, Bayesian methods enable formal combination of expert opinion and objective information into interim and final analyses of clinical trial data. However, most previous Bayesian approaches have based the stopping decision on the posterior probability content of one or more regions of the parameter space, thus implicitly determining a loss and decision structure. In this paper, we offer a fully Bayesian approach to this problem, specifying not only the likelihood and prior distributions but appropriate loss functions as well. At each data monitoring point, we enumerate the available decisions and investigate the use of backward induction, implemented via Monte Carlo methods, to choose the optimal course of action. We then present a forward sampling algorithm that substantially eases the analytic and computational burdens associated with backward induction, offering the possibility of fully Bayesian optimal sequential monitoring for previously untenable numbers of interim looks. We show that forward sampling can always identify the optimal sequential strategy in the case of a one-parameter exponential family with a conjugate prior and monotone loss functions as well as the best member of a certain class of strategies when backward induction is infeasible. Finally, we illustrate and compare the forward and backward approaches using data from a recent AIDS clinical trial.
Assuntos
Biometria/métodos , Ensaios Clínicos como Assunto/estatística & dados numéricos , Técnicas de Apoio para a Decisão , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Anti-Infecciosos/farmacologia , Teorema de Bayes , Método Duplo-Cego , Humanos , Modelos Estatísticos , Pirimetamina/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Toxoplasmose Cerebral/prevenção & controleRESUMO
We studied the effectiveness of performing a stereotactic brain biopsy in the individual with acquired immunodeficiency syndrome (AIDS) and an intracranial mass lesion who failed 2 weeks of antitoxoplasmosis therapy. We used a decision analysis to compare two different treatment strategies: biopsy and no biopsy. The analysis estimates the average life expectancy for each choice and investigates the sensitivity of these results by varying parameters within the model. In the base case analysis (diagnostic yield of biopsy, 0.89; operative mortality, 0.015; life expectancy of lymphoma untreated and treated, 42 and 120 days), the life expectancy of the biopsy strategy was 98 days compared with 67 days for the no-biopsy strategy, for a net survival benefit of 31 days. Sensitivity analyses revealed that the life expectancy of the biopsy strategy remained greater than the no-biopsy strategy for a wide range of variable specifications. The net survival benefit, however, was sensitive to the diagnostic success rate, the operative mortality, the likelihood of a lymphoma diagnosis, and the life expectancy of patients being diagnosed and treated for lymphoma. These data allow AIDS patients and physicians to learn more about the potential outcomes of the alternative management strategies when an individual fails to respond to empiric antitoxoplasmosis therapy.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Biópsia/métodos , Encéfalo/patologia , Técnicas de Apoio para a Decisão , Toxoplasmose Cerebral/etiologia , Toxoplasmose Cerebral/patologia , Árvores de Decisões , Estudos de Avaliação como Assunto , Humanos , Sensibilidade e Especificidade , Técnicas Estereotáxicas , Toxoplasmose Cerebral/tratamento farmacológico , Falha de TratamentoRESUMO
OBJECTIVE: To construct and evaluate a decision analytic model of proposed management strategies for HIV-infected patients presenting with cerebral mass lesions, radiographically compatible with toxoplasmosis, lymphoma, or other etiologies, assuming knowledge of Toxoplasma antibody status in serum. METHODS: Using decision analysis, we evaluated two management strategies, for patients found to be either Toxoplasma-seropositive or -negative, for whom an initial choice was made for early brain biopsy (EB) or for empiric therapy with delayed biopsy (ETDB) of non-responders. The outcome to be optimized was the percentage of patients alive at 12 months. Model variables included predictive value of toxoplasmosis serology, probabilities of treatment response and death within 14-21 days conditional on correct diagnosis, probability of operative death, probabilities of non-diagnostic brain biopsy conditional both on correct diagnosis and prior treatment. RESULTS: One and two-way sensitivity analyses, by Toxoplasma serostatus, led to the following conclusions (1) for Toxoplasma-seropositive patients, ETDB gives nearly equivalent outcomes to EB of all patients; (2) for Toxoplasma-seronegative patients, although both strategies have equivalent outcomes under baseline assumptions, EB is preferred if there are even small survival advantages for early versus delayed diagnosis of lymphoma or other conditions, or if risk of death within 14-21 days of ET exceeds 10% when correct diagnosis is not toxoplasmosis. CONCLUSION: Under plausible assumptions, Toxoplasma-seronegative patients will benefit from an early biopsy strategy.