RESUMO
OBJECTIVE: Despite scaling-up testing and antiretroviral treatment in Latin America, advanced HIV remains a significant public health problem. The objective of the present study was look for historical risk factors for death in French Guiana's HIV cohort taking into account the immunological status, the main opportunistic infections, and their treatment. A retrospective cohort study was conducted on data collected between 1992 and 2008 to identify factors associated with death in a cohort 2323 patients. RESULTS: There were 370 deaths for a total 9608 patient-years. Being on tuberculosis treatment was associated with a greater hazard of death. The diagnosis of confirmed tuberculosis, of histoplasmosis, of toxoplasmosis, and pneumocystosis were independently associated with death. Interactions terms between cotrimoxazole treatment and pneumocystosis, or between confirmed tuberculosis and tuberculosis treatment showed a protective treatment-effect. All patients having received anti-tuberculosis treatment (n = 347) did not have a final diagnosis of tuberculosis (n = 93). For histoplasmosis, 199 patients received antifungal treatment while 141 were diagnosed as having histoplasmosis. The number of patients on anti-tuberculosis drugs was far greater that the number of patients with confirmed tuberculosis, and these patients on treatment without confirmed tuberculosis had a twofold greater risk of dying.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Infecções por HIV/mortalidade , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/mortalidade , Adulto , Antituberculosos , Comorbidade , Feminino , Guiana Francesa/epidemiologia , Histoplasmose/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/mortalidade , Estudos Retrospectivos , Toxoplasmose/mortalidadeRESUMO
The aim of our study was to describe the clinical features, the etiologies, and the factors associated with poor outcome of encephalitis in French Guiana. Our study was retrospective, including all cases of encephalitis hospitalized in the Cayenne General Hospital, from January 2007 to July 2017. Patients were included through the 2013 encephalitis consortium criteria and the outcome was evaluated using the Glasgow outcome scale at 3 months from the diagnosis of encephalitis. We included 108 patients, giving an approximate incidence rate of four cases/100,000 inhabitants/year. The origin of the encephalitis was diagnosed in 81 cases (75%), and 72 of them (66.7%) were from an infectious origin. The most common infectious causes were Cryptococcus sp. (18.5%) independently of the immune status, Toxoplasma gondii (13.9%), and Streptococcus pneumoniae (5.5%). In the follow-up, 48 patients (46.6%) had poor outcome. Independent risk factors associated with poor outcome at 3 months were "coming from inside area of the region" (P = 0.036, odds ratio [OR] = 4.19; CI 95% = 1.09-16.06), need for mechanical ventilation (P = 0.002, OR = 5.92; CI 95% = 1.95-17.95), and age ≥ 65 years (P = 0.049, OR = 3.99; CI 95% = 1.01-15.89). The most identified cause of encephalitis in French Guiana was Cryptococcus. The shape of the local epidemiology highlights the original infectious situation with some local specific pathogens.
Assuntos
Criptococose/epidemiologia , Encefalite/epidemiologia , Meningoencefalite/epidemiologia , Infecções Pneumocócicas/epidemiologia , Toxoplasmose/epidemiologia , Adolescente , Adulto , Criptococose/microbiologia , Criptococose/mortalidade , Cryptococcus/isolamento & purificação , Cryptococcus/patogenicidade , Encefalite/microbiologia , Encefalite/mortalidade , Encefalite/parasitologia , Feminino , Guiana Francesa/epidemiologia , Escala de Resultado de Glasgow , Humanos , Incidência , Masculino , Meningoencefalite/microbiologia , Meningoencefalite/mortalidade , Meningoencefalite/parasitologia , Pessoa de Meia-Idade , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/mortalidade , Respiração Artificial , Estudos Retrospectivos , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pneumoniae/patogenicidade , Análise de Sobrevida , Toxoplasma/isolamento & purificação , Toxoplasma/patogenicidade , Toxoplasmose/mortalidade , Toxoplasmose/parasitologiaRESUMO
A majority of emerging infectious diseases in humans are zoonoses. Understanding factors that influence the emergence and transmission of zoonoses is pivotal for their prevention and control. Toxoplasma gondii is one of the most widespread zoonotic pathogens known today. Whereas only a few genotypes of T. gondii dominate in the Northern Hemisphere, many genotypes coexist in South America. Furthermore, T. gondii strains from South America are more likely to be virulent than those from the Northern Hemisphere. However, it is not clear what factor(s) shaped modern-day genetic diversity and virulence of T. gondii Here, our analysis suggests that the rise and expansion of farming in the past 11,000 years established the domestic cat/mouse transmission cycle for T. gondii, which has undoubtedly played a significant role in the selection of certain linages of T. gondii Our mathematical simulations showed that within the domestic transmission cycle, intermediately mouse-virulent T. gondii genotypes have an adaptive advantage and eventually become dominant due to a balance between lower host mortality and the ability to superinfect mice previously infected with a less virulent T. gondii strain. Our analysis of the global type II lineage of T. gondii suggests its Old World origin but recent expansion in North America, which is likely the consequence of global human migration and trading. These results have significant implications concerning transmission and evolution of zoonotic pathogens in the rapidly expanding anthropized environment demanded by rapid growth of the human population and intensive international trading at present and in the future.
Assuntos
Toxoplasma/genética , Toxoplasma/patogenicidade , Toxoplasmose/genética , Toxoplasmose/transmissão , Zoonoses/genética , Zoonoses/transmissão , Animais , Gatos , Migração Humana , Humanos , Camundongos , América do Sul , Toxoplasmose/mortalidade , Zoonoses/mortalidadeRESUMO
Activation of the purinergic P2X7 receptor by extracellular ATP (eATP) potentiates proinflammatory responses during infections by intracellular pathogens. Extracellular ATP triggers an antimicrobial response in macrophages infected with Toxoplasma gondii in vitro, suggesting that purinergic signaling may stimulate host defense mechanisms against toxoplasmosis. Here, we provide in vivo evidence in support of this hypothesis, by showing that P2X7-/- mice are more susceptible than P2X7+/+ mice to acute infection by the RH strain of T. gondii, and that this phenomenon is associated with a deficient proinflammatory response. Four days post-infection, peritoneal washes from infected P2X7-/- mice had no or little increase in the levels of the proinflammatory cytokines IL-12, IL-1ß, IFN-γ, and TNF-α, whose levels increased markedly in samples from infected P2X7+/+ mice. Infected P2X7-/- mice displayed an increase in organ weight and histological alterations in some of the 'shock organs' in toxoplasmosis - the liver, spleen and mesenteric lymph nodes. The liver of infected P2X7-/- mice had smaller granulomas, but increased parasite load/granuloma. Our results confirm that the P2X7 receptor is involved in containing T. gondii spread in vivo, by stimulating inflammation.
Assuntos
Receptores Purinérgicos P2X7/metabolismo , Toxoplasma/imunologia , Toxoplasmose/imunologia , Toxoplasmose/metabolismo , Animais , Biópsia , Citocinas/metabolismo , Feminino , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/parasitologia , Mediadores da Inflamação/metabolismo , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Linfonodos/imunologia , Linfonodos/metabolismo , Linfonodos/patologia , Masculino , Camundongos , Camundongos Knockout , Carga Parasitária , Baço/imunologia , Baço/metabolismo , Baço/patologia , Toxoplasmose/mortalidade , Toxoplasmose/parasitologia , Toxoplasmose AnimalRESUMO
This study investigated the genetic features of Toxoplasma gondii isolated directly in autopsies of HIV-infected patients who died with severe disseminated toxoplasmosis. This retrospective analysis was conducted in a cohort of 15 HIV-infected patients with clinical and laboratory data. They had previous cerebral toxoplasmosis at least 6 months before the disseminated toxoplasmosis episode. The hypothesis was that they were infected with highly virulent parasites due to the condition in which they died. T. gondii genotyping was done directly in DNA extracted from 30 autopsy brain and lung samples (2 per patient) and mutilocus PCR-RFLP genotyping was done using 12 molecular markers. The 30 clinical samples were genotyped successfully in 8 or more loci and six suggestive genotypes were identified. One of them was Toxo DB #11, previously identified in different domestic animals and virulent in experimental animals. The other five suggestive genotypes identified in 14 patients were not described. TgHuDis1 was the most frequent and was determined in 8 patients. TgHuDis3 and TgHuDis5 were identified in two patients each. TgHuDis2 and TgHuDis4 have been identified in one patient each. These suggestive genotypes could be considered as virulent, since they caused severe tissue damage and had similar characteristics as Toxo # DB 11.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Toxoplasma/classificação , Toxoplasmose/mortalidade , Síndrome da Imunodeficiência Adquirida/mortalidade , Síndrome da Imunodeficiência Adquirida/patologia , Adulto , Autopsia , Encéfalo/parasitologia , Encéfalo/patologia , Brasil , Estudos de Coortes , DNA de Protozoário/química , DNA de Protozoário/isolamento & purificação , Feminino , Fixadores , Formaldeído , Técnicas de Genotipagem , Humanos , Imuno-Histoquímica , Pulmão/parasitologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Estudos Retrospectivos , Toxoplasma/genética , Toxoplasmose/parasitologia , Toxoplasmose/patologia , Adulto JovemRESUMO
The interleukin (IL)-2R alpha chain (CD25) is expressed on regulatory T cells (Treg), which constitute more than 85% of the CD25+ T cell population in a naïve mouse. CD25 is also expressed on effector T cells in mice suffering from an acute infection by the obligate intracellular protozoan parasite, Toxoplasma gondii. Lethal toxoplasmosis is accompanied by a significant loss of Treg in mice naturally susceptible to toxoplasmosis. The present study was done to explore the role of Treg cells using an anti-CD25 antibody-mediated depletion in mice naturally resistant to toxoplasmosis. Although a significant decrease in the percentage of Treg cells was observed following anti-CD25 monoclonal antibody injections, the depletion of CD25+ cells during acute toxoplasmosis did not significantly increase the mortality of Swiss OF1 mice and no significant difference was observed in the brain parasitic load between the mice in the depleted-infected and isotype-infected groups. We found no significant difference between the titres of total IgG in the sera of the mice from the two groups in the chronic phase. However, CD25+ cells depletion was followed by significantly higher levels of IL-12 in the serum of depleted mice than in that of mice injected with the isotype control antibody.
Assuntos
Anticorpos Monoclonais/imunologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Linfócitos T Reguladores/citologia , Toxoplasma/imunologia , Toxoplasmose/imunologia , Doença Aguda , Animais , Feminino , Camundongos , Carga Parasitária , Linfócitos T Reguladores/imunologia , Toxoplasmose/mortalidade , Toxoplasmose/patologiaRESUMO
The interleukin (IL)-2R alpha chain (CD25) is expressed on regulatory T cells (Treg), which constitute more than 85 percent of the CD25+ T cell population in a naïve mouse. CD25 is also expressed on effector T cells in mice suffering from an acute infection by the obligate intracellular protozoan parasite, Toxoplasma gondii. Lethal toxoplasmosis is accompanied by a significant loss of Treg in mice naturally susceptible to toxoplasmosis. The present study was done to explore the role of Treg cells using an anti-CD25 antibody-mediated depletion in mice naturally resistant to toxoplasmosis. Although a significant decrease in the percentage of Treg cells was observed following anti-CD25 monoclonal antibody injections, the depletion of CD25+ cells during acute toxoplasmosis did not significantly increase the mortality of Swiss OF1 mice and no significant difference was observed in the brain parasitic load between the mice in the depleted-infected and isotype-infected groups. We found no significant difference between the titres of total IgG in the sera of the mice from the two groups in the chronic phase. However, CD25+ cells depletion was followed by significantly higher levels of IL-12 in the serum of depleted mice than in that of mice injected with the isotype control antibody.
Assuntos
Animais , Feminino , Camundongos , Anticorpos Monoclonais/imunologia , /imunologia , Linfócitos T Reguladores/citologia , Toxoplasma/imunologia , Toxoplasmose/imunologia , Doença Aguda , Carga Parasitária , Linfócitos T Reguladores/imunologia , Toxoplasmose/mortalidade , Toxoplasmose/patologiaRESUMO
Atypical Toxoplasma gondii strains, unrelated to archetypal clonal lineages (I, II, III), have been reported more frequently over the last decade in areas other than Europe and North America. A newly described form of toxoplasmosis, 'Amazonian toxoplasmosis' (AT), has been reported since 2002 in French Guiana. It is characterized by severe cases and atypical strains linked to a neotropical forest-based cycle. We report on the cases of AT that required intensive care management. We performed a prospective observational study on hospitalized adults in the Intensive Care Unit (ICU) from 2002 to 2008. Clinical and laboratory data, microbiological findings and outcomes were recorded. Data, including the ICU simplified acute physiology score and the pneumonia severity index, were calculated. Epidemiological risk factors for AT were assessed through questionnaires. Eleven non-immunodeficient patients were admitted to the ICU in Cayenne for life-threatening pneumonia associated with disseminated toxoplasmosis. Mechanical ventilation was necessary in seven patients, four of whom required immediate orotracheal intubation. Cardiac and ophthalmological abnormalities were found in five and four patients, respectively. One patient died from multiple organ failure. The genetic characterization of Toxoplasma DNA using six microsatellite markers revealed unique and atypical genotypes in eight patients. All patients presented epidemiological risk factors for AT. In French Guiana, significant T. gondii-related infectious syndrome associated with the lungs, a high level of LDH activity and the reported risk factors for AT was strongly suggestive of disseminated toxoplasmosis with a possible trend toward life-threatening pneumonia.
Assuntos
Toxoplasma/isolamento & purificação , Toxoplasmose/patologia , Adolescente , Adulto , DNA de Protozoário/genética , Feminino , Guiana Francesa/epidemiologia , Genótipo , Humanos , Unidades de Terapia Intensiva , Masculino , Repetições de Microssatélites , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Inquéritos e Questionários , Análise de Sobrevida , Toxoplasma/classificação , Toxoplasma/genética , Toxoplasmose/epidemiologia , Toxoplasmose/mortalidade , Toxoplasmose/parasitologia , Adulto JovemRESUMO
The aim of this study was to assess the effects of a synbiotic composed of Bifidobacterium animalis and fructooligosaccharides on female rats infected with Toxoplasma gondii. Female Wistar rats, treated or not with dexamethasone, were daily supplemented with synbiotics for 21 days. After 15 days of supplementation, the rats were orally infected with 10(4)T. gondii bradyzoites. Blood samples were collected to measure the levels of IFN-γ, IL-10 and T. gondii antibodies. All synbiotic-supplemented rats survived until the end of the experiment; however, non-supplemented dexamethasone-treated rats died between the fifth and the eighth days after T. gondii infection. Dexamethasone-treated rats supplemented with synbiotics (P<0.05) were capable of synthesizing IFN-γ, and this immunological response was essential to ensure their survival. In addition, brain cysts were found in one rat not supplemented with synbiotics. Results suggest that the synbiotic composed of B. animalis and fructooligosaccharides may be beneficial to toxoplasmosis control.
Assuntos
Bifidobacterium/imunologia , Simbióticos , Toxoplasmose/imunologia , Toxoplasmose/prevenção & controle , Animais , Anti-Inflamatórios/farmacologia , Anticorpos Antiprotozoários/sangue , Encéfalo/parasitologia , Dexametasona/farmacologia , Feminino , Sistema Imunitário/efeitos dos fármacos , Interferon gama/sangue , Interleucina-10/sangue , Ratos , Ratos Wistar , Análise de Sobrevida , Toxoplasma/fisiologia , Toxoplasmose/mortalidadeRESUMO
Pulmonary toxoplasmosis is a challenging diagnosis in immunosuppressed patients with nonspecific clinical picture and radiologic findings. We present a case of pneumonia due to Toxoplasma gondii diagnosed by polymerase chain reaction (PCR) in the bronchoalveolar lavage (BAL) fluid of a patient with acquired immunodeficiency syndrome (AIDS). Coinfection with Pneumocystis jirovecii was found in the same specimen. Direct examination and culture for bacteria, mycobacteria and other fungus were negative. Despite the intensive management, respiratory compromise evolved rapidly, with the need for ventilatory support. Acute respiratory distress syndrome developed, and the patient died of multiple organ failure. This case illustrates that a high index of suspicion is necessary for diagnosis of pulmonary toxoplasmosis, a potentially fatal condition. Due to high diagnostic performance, PCR in BAL fluid should be included in the evaluation of immunosuppressed patients with nonspecific pulmonary diseases.
O diagnóstico de toxoplasmose pulmonar em pacientes imunossuprimidos é difícil, devido ao quadro clínico e aos achados radiológicos inespecíficos. Neste artigo, relatamos o caso de uma paciente com síndrome da imunodeficiência adquirida (SIDA), que apresentou pneumonia por Toxoplasma gondii diagnosticada através de reação em cadeia da polimerase (PCR) no lavado bronco-alveolar (LBA). A paciente apresentava co-infecção com Pneumocystis jirovecii. Os demais exames microbiológicos, como bacterioscópico, cultural para bactérias, micobactérias e fungos, foram negativos. Apesar do manejo intensivo, a paciente evoluiu com síndrome do desconforto respiratório agudo e óbito por falência múltipla dos órgãos. Este caso demonstra que um alto índice de suspeita clínica é necessário para o diagnóstico de pneumonia por Toxoplasma gondii. Devido ao seu desempenho diagnóstico, o PCR para Toxoplasma gondii no LBA deve ser incluído na avaliação de pacientes imunossuprimidos com quadros pulmonares inespecíficos.