RESUMO
The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV-1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short-term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long-term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first- and second-line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART 'pipeline' of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained
Assuntos
Humanos , Criança , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Terapia Antirretroviral de Alta AtividadeRESUMO
Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) may represent a serious public health problem, owing to the spread of toxin-producing lineages. The presence of genes encoding for Panton-Valentine leukocidin (PVL) is an important virulence marker, as the clinical sequelae of PVL-positive infections are often described as more severe than those of PVL-negative S. aureus infections. To date, the presence of PVL has not appeared to be common in Italy; we describe the intrafamilial transmission of an epidemic PVL-producing CA-MRSA lineage, Southwest Pacific clone (SWP). Our data suggested that the strain circulated from the father, who was recurrently affected by a soft tissue infection, to the mother, who showed nasal colonization, and to their child, who was hospitalized with symptoms of necrotizing pneumonia. In this case, we found that a recurrent skin infection that is not normally taken into account may represent a serious threat if caused by a PVL-producing strain. Our findings may have considerable implications for strategies for infection control and treatment of methicillin-resistant S. aureus infections.
Assuntos
Toxinas Bacterianas/genética , Exotoxinas/genética , Leucocidinas/genética , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Pneumonia Estafilocócica/transmissão , Infecções Estafilocócicas/transmissão , Infecções Cutâneas Estafilocócicas/transmissão , Toxinas Bacterianas/metabolismo , Brasil/etnologia , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/transmissão , Exotoxinas/metabolismo , Pai , Humanos , Lactente , Itália/epidemiologia , Leucocidinas/metabolismo , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/metabolismo , Mães , Pneumonia Estafilocócica/microbiologia , Recidiva , Infecções dos Tecidos Moles/microbiologia , Infecções Estafilocócicas/microbiologia , Fatores de Virulência/genéticaRESUMO
Trastuzumab is an important biological agent in the treatment of HER2-positive breast cancer, with effects on response rates, progression-free survival, overall survival and quality of life. Although this drug is well tolerated in terms of adverse effects, trastuzumab-associated myocardiotoxicity has been described to have an incidence of 0.6-4.5% and in rare cases, the drug can trigger severe congestive heart failure with progression to death or even mimic acute coronary syndrome with complete left bundle branch blockade. In this paper is reported a case of trastuzumab-associated myocardiotoxicity manifesting as acute coronary syndrome in a 69-year-old female. The patient is currently undergoing a conservative clinical treatment that restricts overexertion.The majority of clinical studies report trastuzumab-induced cardiotoxicity as a rare event, and, when present, characterized by mild to moderate clinical signs, the ease of reversibility with pharmacological measures and the temporary discontinuation of the medication. Conversely, it is vital for the oncologist/cardiologist to consider the possibility that trastuzumab-induced cardiotoxicity may manifest itself as a severe clinical case, mimicking acute coronary syndrome, justifying careful risk stratification and adequate cardiac monitoring, especially in high-risk patients.
RESUMO
The non-O157 Shiga toxin-producing Escherichia coli (STEC) contamination in carcasses and feces of 811 bovines in nine beef abattoirs from Argentina was analyzed during a period of 17 months. The feces of 181 (22.3%) bovines were positive for non-O157 STEC, while 73 (9.0%) of the carcasses showed non-O157 STEC contamination. Non-O157 STEC strains isolated from feces (227) and carcasses (80) were characterized. The main serotypes identified were O178:H19, O8:H19, O130:H11, and O113:H21, all of which have produced sporadic cases of hemolytic-uremic syndrome in Argentina and worldwide. Twenty-two (7.2%) strains carried a fully virulent stx/eae/ehxA genotype. Among them, strains of serotypes O103:[H2], O145:NM, and O111:NM represented 4.8% of the isolates. Xba I pulsed-field gel electrophoresis pattern analysis showed 234 different patterns, with 76 strains grouped in 30 clusters. Nine of the clusters grouped strains isolated from feces and from carcasses of the same or different bovines in a lot, while three clusters were comprised of strains distributed in more than one abattoir. Patterns AREXSX01.0157, AREXBX01.0015, and AREXPX01.0013 were identified as 100% compatible with the patterns of one strain isolated from a hemolytic-uremic syndrome case and two strains previously isolated from beef medallions, included in the Argentine PulseNet Database. In this survey, 4.8% (39 of 811) of the bovine carcasses appeared to be contaminated with nonO157 STEC strains potentially capable of producing sporadic human disease, and a lower proportion (0.25%) with strains able to produce outbreaks of severe disease.
Assuntos
Matadouros , Bovinos/microbiologia , Qualidade de Produtos para o Consumidor , Contaminação de Alimentos/análise , Escherichia coli Shiga Toxigênica/isolamento & purificação , Animais , Argentina/epidemiologia , DNA Bacteriano/análise , Surtos de Doenças/prevenção & controle , Fezes/microbiologia , Feminino , Contaminação de Alimentos/prevenção & controle , Genótipo , Síndrome Hemolítico-Urêmica/epidemiologia , Síndrome Hemolítico-Urêmica/prevenção & controle , Humanos , Masculino , Prevalência , Medição de Risco , Sorotipagem , Escherichia coli Shiga Toxigênica/classificação , Pele/microbiologiaRESUMO
In Argentina, Escherichia coli O157:H7/NM (STEC O157) is the prevalent serotype associated with hemolytic uremic syndrome (HUS), which is endemic in the country with more than 400 cases per year. In order to estimate the prevalence and characteristics of STEC O157 in beef cattle at slaughter, a survey of 1,622 fecal and carcass samples was conducted in nine beef exporting abattoirs from November 2006 to April 2008. A total of 54 samples were found positive for STEC O157, with an average prevalence of 4.1% in fecal content and 2.6% in carcasses. Calves and heifers presented higher percentages of prevalence in feces, 10.5 and 8.5%, respectively. All STEC O157 isolates harbored stx(2) (Shiga toxin 2), eae (intimin), ehxA (enterohemolysin), and fliC(H7) (H7 flagellin) genes, while stx(1) (Shiga toxin 1) was present in 16.7% of the strains. The prevalent (56%) stx genotype identified was stx(2) combined with variant stx(2c (vh-a)), the combination of which is also prevalent (>90%) in STEC O157 post-enteric HUS cases in Argentina. The clonal relatedness of STEC O157 strains was established by phage typing and pulsed-field gel electrophoresis (PFGE). The 54 STEC isolates were categorized into 12 different phage types and in 29 XbaI-PFGE patterns distributed in 27 different lots. STEC O157 strains isolated from 5 of 21 carcasses were identical by PFGE (100% similarity) to strains of the fecal content of the same or a contiguous bovine in the lot. Five phage type-PFGE-stx profiles of 10 strains isolated in this study matched with the profiles of the strains recovered from 18 of 122 HUS cases that occurred in the same period.
Assuntos
Matadouros , Bovinos/microbiologia , Escherichia coli O157 , Fezes/microbiologia , Toxinas Shiga/biossíntese , Animais , Argentina/epidemiologia , Tipagem de Bacteriófagos , Análise por Conglomerados , Contagem de Colônia Microbiana , Qualidade de Produtos para o Consumidor , DNA Bacteriano/análise , Escherichia coli O157/classificação , Escherichia coli O157/genética , Escherichia coli O157/isolamento & purificação , Escherichia coli O157/metabolismo , Genótipo , Síndrome Hemolítico-Urêmica/epidemiologia , Síndrome Hemolítico-Urêmica/microbiologia , Humanos , Epidemiologia Molecular , Fenótipo , Prevalência , Toxinas Shiga/genéticaRESUMO
Shiga toxin-producing Escherichia coli is an emergent pathogen, being the Shiga toxin (Stx) the main virulence factor. These toxins are classified into 6 types (1,2, 2c, 2d, 2e and 2f) and 22 variants. In Argentina, two PCR for stx gene detection, PCR-MK and multiplex-PCR, were validated. The aim of this work was to analyze, by using bioinformatic tools, the stx variants that could be amplified by these PCRs, and to experimentally show the amplification of 8 stx variants. Twenty-five nucleotide sequences were collected from GenBank corresponding to 21 stx variants. The BLAST 2 sequences program was used to analyze the complementarities between the nucleotide sequence of the variants and the primers corresponding to the PCR studied. PCR-MK could detect types stx1, stx2, stx2c, stx2d and stx2f, but not type stx2e and three type stx2c variants. On the other hand, the multiplex-PCR could detect types stx1, stx2, stx2c, stx2d, but not stx2e and stx2f types. It was experimentally determined that both PCRs can detect those variants that cause severe disease in humans.
Assuntos
Reação em Cadeia da Polimerase/métodos , Toxina Shiga/genética , Toxina Shiga/isolamento & purificação , Biologia Computacional , Toxina Shiga/classificaçãoRESUMO
Escherichia coli productor de toxina Shiga es un patógeno emergente cuyo principal factor de virulencia son las toxinas Shiga (Stx), codificadas por los genes stx. Estas toxinas se clasifican en 6 tipos (1, 2, 2c, 2d, 2e y 2f) que agrupan a 22 variantes. En Argentina se validaron dos técnicas de PCR para la detección de los genes stx, PCR-MK y PCR múltiple. Los objetivos del trabajo fueron analizar mediante el uso de herramientas bioinformáticas la capacidad de dichas técnicas para detectar las variantes del gen stx y demostrar experimentalmente la amplificación de 8 variantes stx. Se recopilaron 25 secuencias nucleotídicas de la base de datos GenBank correspondientes a 21 variantes de stx. Se utilizó el programa BLAST 2 sequences para analizar la complementariedad de las bases nucleotídicas entre las secuencias de las variantes y las secuencias de los cebadores utilizados en las PCR estudiadas. La técnica de PCR-MK permite detectar los tipos stx1, stx2, stx2c, stx2d y stx2f, aunque no permite detectar el tipo stx2e y tres variantes del tipo stx2c. La PCR múltiple permite detectar los tipos stx1, stx2, stx2c, stx2d, pero no los tipos stx2e y stx2f. Se demostró experimentalmente que ambas técnicas de PCR son apropiadas para la detección de las variantes que están asociadas a enfermedad grave en el hombre.
Shiga toxin-producing Escherichia coli is an emergent pathogen, being the Shiga toxin (Stx) the main virulence factor. These toxins are classified into 6 types (1, 2, 2c, 2d, 2e and 2f) and 22 variants. In Argentina, two PCR for stx gene detection, PCR-MK and multiplex-PCR, were validated. The aim of this work was to analyze, by using bioinformatic tools, the stx variants that could be amplified by these PCRs, and to experimentally show the amplification of 8 stx variants. Twentyfive nucleotide sequences were collected from GenBank corresponding to 21 stx variants. The BLAST 2 sequences program was used to analyze the complementarities between the nucleotide sequence of the variants and the primers corresponding to the PCR studied. PCR-MK could detect types stx1, stx2, stx2c, stx2d and stx2f, but not type stx2e and three type stx2c variants. On the other hand, the multiplex-PCR could detect types stx1, stx2, stx2c, stx2d, but not stx2e and stx2f types. It was experimentally determined that both PCRs can detect those variants that cause severe disease in humans.
Assuntos
Reação em Cadeia da Polimerase/métodos , Toxina Shiga/genética , Toxina Shiga/isolamento & purificação , Biologia Computacional , Toxina Shiga/classificaçãoRESUMO
Several lines of evidence have suggested that renal handling of proteins in rats with several nephropathies may contribute to the tubulointerstitial damage observed in these animals. It has been suggested that proteins filtered by the glomeruli may be toxic for tubule cells. The aim of this study was to investigate the relationship between albuminuria and tubular lesions observed in rats during the first two weeks after treatment with adriamycin (AD). Thirty female Wistar rats were injected intravenously with adriamycin at the dose of 3.5 (17 rats) or 5mg/kg body weight (13 rats), and 7 were injected with 0.15 M NaCl (control group). Seven days later, we replaced drinking water with a 0.10 M sodium bicarbonate solution for 6 of the animals injected with 5 mg/kg adriamycin (group AD-B). Urine samples were collected before and 7 and 15 days after treatment to quantify albumin. The rats were killed 7 and 18 days after the injections, and the kidneys removed for immunohistochemical study. We observed a significant increase in urinary albumin excretion 15 days after AD injection (3.5 mg/kg), but not 7 days after AD. However, in the animals injected with 5.0 mg/kg AD (group AD-5) the increase in albuminuria was observed as early as on day 7. The immunohistochemical studies showed increased vimentin and albumin immunoreaction in the tubular cells of the renal cortex from the kidneys of rats injected with 3.5 mg/kg (group AD-3) only 18 days after treatment (p < 0.05), whereas in the animals treated with 5 mg/kg AD these immunohistochemical alterations were more intense. However, treatment with sodium bicarbonate attenuated the tubular lesions and reduced albumin reabsorption in adriamycin-treated rats. In conclusion, these experiments showed a relationship between albuminuria and tubular lesions in adriamycin-treated rats.
Assuntos
Albuminúria/induzido quimicamente , Túbulos Renais/patologia , Nefrite Intersticial/patologia , Análise de Variância , Animais , Creatinina/sangue , Creatinina/urina , Técnicas de Cultura , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Doxorrubicina , Feminino , Imuno-Histoquímica , Injeções Intravenosas , Testes de Função Renal , Túbulos Renais/efeitos dos fármacos , Probabilidade , Ratos , Ratos Wistar , Valores de Referência , Sensibilidade e EspecificidadeRESUMO
Neutrophil, lymphocyte, and T-cell subset numbers and immunoglobulin levels were evaluated at birth to age 2 years in 675 children born to mothers infected with the human immunodeficiency virus type 1 (58 infected symptom-free subjects (P-1), 203 infected subjects with symptoms (P-2), and 414 uninfected subjects). The P-2 patients had (even at birth to age 1 month) lower CD4+ lymphocyte and higher IgA and IgM values than P-1 and uninfected children had. Increased IgG values (from 1 to 6 months of age) and increased CD8+ lymphocyte numbers (at 13 to 24 months of age) were also observed. The P-1 children differed from uninfected children only at 13 to 24 months of age (decreased CD4+ and increased CD8+ lymphocytes). Progressive immunologic changes were found in P-2 patients who had severe clinical conditions and in those who died. To evaluate the predictive meaning of the immunologic changes, we selected 164 children (25 P-2, 15 P-1, and 124 uninfected children) because they had been examined sequentially from birth and they were classified as in the indeterminate state of infection (P-0) at immunologic evaluations at birth to age 1 and at 1 to 6 months of age. During the 1- to 6-month period, P-2 patients had higher immunoglobulin and lower CD4+ lymphocyte values than P-1 and uninfected children had; no difference was found between P-1 and uninfected subjects. These results indicate that in infants with perinatal human immunodeficiency virus type 1 infection, immunologic abnormalities correlate with the clinical condition and are predictive of the clinical outcome rather than the infection status.