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1.
Rev Med Suisse ; 15(671): 2105-2108, 2019 Nov 13.
Artigo em Francês | MEDLINE | ID: mdl-31742942

RESUMO

Screening for latent tuberculosis infection (LTI) is recommended in immunosuppressed patients due to an increased risk of progression from LTI to active tuberculosis. Screening involves indirect immunological tests such as the tuberculin skin test (TST) and the interferon-y release assays (IGRAs). IGRAs seem to show superior performance compared to TST in screening for LTI. However, their use and interpretation in immunosuppressed patients is questionable, particularly because of an increased number of false negative or indeterminate results and a low agreement between tests. Presently, there are no swiss national recommendations for their use in immunosuppressed -patients, except for candidates to anti-TNF treatment.


Assuntos
Hospedeiro Imunocomprometido , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/microbiologia , Tuberculose Latente/complicações , Tuberculose Latente/diagnóstico , Humanos , Testes de Liberação de Interferon-gama , Sensibilidade e Especificidade , Teste Tuberculínico , Fator de Necrose Tumoral alfa/antagonistas & inibidores
3.
Infection ; 47(1): 87-93, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30194635

RESUMO

BACKGROUND: Primary immunodeficiency (PID) in adults is rare and mostly revealed by infections. MATERIAL AND METHODS: Adults without predisposing factors who were admitted to an intensive care unit (ICU) for infection were screened for PID. RESULTS: Six PID cases were diagnosed, mostly revealed by encapsulated bacterial infections. CONCLUSION: Investigation of PID after ICU discharge should be considered to improve early detection.


Assuntos
Infecções Bacterianas/epidemiologia , Síndromes de Imunodeficiência/epidemiologia , Adulto , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Feminino , França/epidemiologia , Hospitalização , Humanos , Síndromes de Imunodeficiência/microbiologia , Unidades de Terapia Intensiva , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Estudos Retrospectivos , Adulto Jovem
4.
Nat Med ; 24(12): 1815-1821, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30397357

RESUMO

Human microbiome studies have revealed the intricate interplay of host immunity and bacterial communities to achieve homeostatic balance. Healthy skin microbial communities are dominated by bacteria with low viral representation1-3, mainly bacteriophage. Specific eukaryotic viruses have been implicated in both common and rare skin diseases, but cataloging skin viral communities has been limited. Alterations in host immunity provide an opportunity to expand our understanding of microbial-host interactions. Primary immunodeficient patients manifest with various viral, bacterial, fungal, and parasitic infections, including skin infections4. Dedicator of cytokinesis 8 (DOCK8) deficiency is a rare primary human immunodeficiency characterized by recurrent cutaneous and systemic infections, as well as atopy and cancer susceptibility5. DOCK8, encoding a guanine nucleotide exchange factor highly expressed in lymphocytes, regulates actin cytoskeleton, which is critical for migration through collagen-dense tissues such as skin6. Analyzing deep metagenomic sequencing data from DOCK8-deficient skin samples demonstrated a notable increase in eukaryotic viral representation and diversity compared with healthy volunteers. De novo assembly approaches identified hundreds of novel human papillomavirus genomes, illuminating microbial dark matter. Expansion of the skin virome in DOCK8-deficient patients underscores the importance of immune surveillance in controlling eukaryotic viral colonization and infection.


Assuntos
Fatores de Troca do Nucleotídeo Guanina/genética , Síndromes de Imunodeficiência/virologia , Dermatopatias/virologia , Pele/virologia , Adolescente , Bacteriófagos/genética , Criança , Feminino , Genoma Viral/genética , Fatores de Troca do Nucleotídeo Guanina/deficiência , Voluntários Saudáveis , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Imunidade/genética , Síndromes de Imunodeficiência/microbiologia , Síndromes de Imunodeficiência/patologia , Linfócitos/virologia , Masculino , Metagenoma/genética , Metagenoma/imunologia , Microbiota/genética , Papillomaviridae/isolamento & purificação , Papillomaviridae/patogenicidade , Pele/microbiologia , Dermatopatias/genética , Dermatopatias/microbiologia , Dermatopatias/patologia
5.
BMC Infect Dis ; 18(1): 367, 2018 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-30081818

RESUMO

BACKGROUND: Aspergillosis is a serious infection particularly affecting the immunodeficient host. Its co-infection with tuberculosis and cytomegalovirus has not been reported before. Embolic events are well recognized with aspergillous endocarditis and aortitis. Splenic abscess is a rare serious complication of disseminated aspergillosis and is difficult to treat. We report the first case of multiple embolic events and splenic abscess in a patient with pulmonary aspergillosis and cytomegaloviral and tuberculous co-infection, without endocarditis or aortitis. CASE PRESENTATION: Thirty-year-old male presented with fever and non-productive cough while on glucocorticoids for glomerulonephritis. He was found to have pulmonary aspergillosis and subsequently developed bilateral lower limb and cerebral fungal emboli and fungal abscess in the spleen. He had IgM and B cell deficiency and cytomegalovirus (CMV) and tuberculous co-infections. He recovered after prolonged course of antimicrobials, splenectomy and cessation of glucocorticoid therapy which also lead to the resolution of immune deficiencies. CONCLUSION: This report illustrates rare combination of B and T cell suppressive effects of glucocorticoids leading to co-infections with CMV, Mycobacterium tuberculosis and Aspergillus and systemic fungal embolization from pulmonary aspergillosis.


Assuntos
Infecções por Citomegalovirus/tratamento farmacológico , Imunossupressão/efeitos adversos , Aspergilose Pulmonar/tratamento farmacológico , Esplenopatias/microbiologia , Tuberculose/tratamento farmacológico , Abscesso Abdominal/tratamento farmacológico , Abscesso Abdominal/microbiologia , Abscesso Abdominal/cirurgia , Adulto , Anti-Infecciosos/uso terapêutico , Linfócitos B/imunologia , Linfócitos B/patologia , Coinfecção , Embolia/microbiologia , Embolia/terapia , Febre/etiologia , Glucocorticoides/efeitos adversos , Humanos , Síndromes de Imunodeficiência/microbiologia , Masculino , Aspergilose Pulmonar/complicações , Embolia Pulmonar/microbiologia , Esplenectomia , Esplenopatias/tratamento farmacológico , Esplenopatias/cirurgia , Tuberculose/microbiologia
7.
Clin Ther ; 40(6): 918-924.e2, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29807668

RESUMO

PURPOSE: Invasive aspergillosis (IA) remains a critical issue in immunosuppressed patients. Detection of galactomannan antigen (GM) in serum samples is included as a criterion of IA by the European Organization for the Research and Treatment of Cancer/Mycoses Study Group. Nevertheless, Aspergillus DNA detection by polymerase chain reaction (PCR) has not yet been included because clinical data validation is lacking. The present study describes the simultaneous performance of GM and PCR tests as routine methods for IA diagnosis. METHODS: During the period January 2012 to December 2017, a total of 156 white children hospitalized in a tertiary children's hospital of Athens (97 boys and 59 girls; age range, 5 months-14 years) were examined as possible cases of IA. Patients were classified into 4 groups based on their underlying diseases: hematologic malignancies (107 of 156 [68.6%]), solid tumors (16 of 156 [10.2%]), primary immunodeficiency (12 of 156 [7.7%]), and hereditary immunodeficiency (21 of 156 [13.5%]). GM detection was made with the Platelia Aspergillus Ag kit (Bio-Rad Laboratories, Hercules, California). Sera with a cut-off index ≥0.5 on at least 2 separate blood collections were considered positive. Serum detection of Aspergillus DNA was conducted with real-time PCR MycAssay Aspergillus assay (Myconostica Ltd, Cambridge, United Kingdom). PCR positivity was determined by using a threshold of 38 cycles in at least 1 serum sample. Four or more successive samples per patient were tested. FINDINGS: Overall, 28 of 156 patients (53 of 744 serum samples) were found positive. Eleven patients were positive using both methods (24 samples). Four children were positive only by PCR (6 samples), whereas 13 (23 samples) were positive only with GM in consecutive samples. Agreement of both methods, GM(+)/PCR(+) or GM(-)/PCR(-), was found in 139 patients (90% of total patients) and 715 samples (96.1% of total samples). The agreement of both methods was found: (1) 85% in patients with hematologic malignancies; (2) 100% in patients with solid tumors; (3) 97.5% in patients with primary immunodeficiency; and (4) 98.8% in patients with hereditary immunodeficiency. Overall disagreement was observed in 17 patients, in which the positive result in any of the 2 methods was estimated as true positive in conjunction with radiologic and other clinical findings. IMPLICATIONS: The combination of GM and PCR, provided high diagnostic accuracy in consecutive samples (twice a week). Clinical, radiologic, and other laboratory findings should be taken into consideration in the evaluation of GM and PCR.


Assuntos
Antígenos/sangue , Aspergilose/diagnóstico , Aspergillus/genética , DNA Fúngico/sangue , Mananas/sangue , Adolescente , Aspergilose/sangue , Aspergilose/microbiologia , Criança , Pré-Escolar , Feminino , Grécia , Humanos , Hospedeiro Imunocomprometido , Síndromes de Imunodeficiência/sangue , Síndromes de Imunodeficiência/microbiologia , Lactente , Masculino , Neoplasias/sangue , Neoplasias/microbiologia , Reação em Cadeia da Polimerase em Tempo Real
8.
PLoS One ; 13(4): e0195310, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29617463

RESUMO

BACKGROUND: Inability to maintain a stable and beneficial microbiota is associated with chronic gut inflammation, which classically manifests as colitis but may more commonly exist as low-grade inflammation that promotes metabolic syndrome. Alterations in microbiota, and associated inflammation, can originate from dysfunction in host proteins that manage the microbiota, such as the flagellin receptor TLR5. That the complete absence of a microbiota (i.e. germfree conditions) eliminates all evidence of inflammation in TLR5-deficient mice demonstrates that this model of gut inflammation is microbiota-dependent. We hypothesize that such microbiota dependency reflects an inability to manage pathobionts, such as Adherent-Invasive E. coli (AIEC). Herein, we examined the extent to which microbiota mismanagement and associated inflammation in TLR5-deficient mice would manifest in a limited and pathobiont-free microbiota. For this purpose, WT and TLR5-deficient mice were generated and maintained with the 8-member consortium of bacteria referred to as "Altered Schaedler Flora" (ASF). Such ASF animals were subsequently inoculated with AIEC reference strain LF82. Feces were assayed for bacterial loads, fecal lipopolysaccharide and flagellin loads, fecal inflammatory marker lipocalin-2 and microbiota composition. RESULTS: Relative to similarly maintained WT mice, mice lacking TLR5 (T5KO) did not display low-grade intestinal inflammation nor metabolic syndrome under ASF conditions. Concomitantly, the ASF microbial community was similar between WT and T5KO mice, while inoculation with AIEC strain LF82 resulted in alteration of the ASF community in T5KO mice compared to WT control animals. AIEC LF82 inoculation in ASF T5KO mice resulted in microbiota components having elevated levels of bioactive lipopolysaccharide and flagellin, a modest level of low-grade inflammation and increased adiposity. CONCLUSIONS: In a limited-complexity pathobiont-free microbiota, loss of the flagellin receptor TLR5 does not impact microbiota composition nor its ability to promote inflammation. Addition of AIEC to this ecosystem perturbs microbiota composition, increases levels of lipopolysaccharide and flagellin, but only modestly promotes gut inflammation and adiposity, suggesting that the phenotypes previously associated with loss of this innate immune receptor require disruption of complex microbiota.


Assuntos
Gastroenterite/imunologia , Gastroenterite/microbiologia , Microbioma Gastrointestinal/imunologia , Síndromes de Imunodeficiência/metabolismo , Síndromes de Imunodeficiência/microbiologia , Intestinos/imunologia , Intestinos/microbiologia , Animais , Escherichia coli , Transplante de Microbiota Fecal , Fezes/microbiologia , Feminino , Flagelina/metabolismo , Imunidade Inata , Lipopolissacarídeos/metabolismo , Masculino , Síndrome Metabólica/imunologia , Síndrome Metabólica/microbiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor 5 Toll-Like/deficiência , Receptor 5 Toll-Like/genética
9.
BMJ Case Rep ; 20182018 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-29680795

RESUMO

We present a case of monocytopaenia and mycobacteria-related infection (MonoMac) syndrome in a 30-year-old man of Indian origin. The clinical diagnosis of GATA2 haploinsufficiency was suspected after an unusual neurological presentation on a background of myelodysplastic syndrome and childhood pulmonary tuberculosis. The patient had a longitudinally extensive spinal cord lesion and a lesion in the medulla. No obvious infective cause for the spinal cord MRI abnormality was found, and the lesions were presumed to be inflammatory in nature. The family history consisted of autosomal dominant clinical features suggestive of GATA2 haploinsufficiency. Genetic testing in peripheral leucocytes revealed a pathogenic mutation in GATA2 This is the first-ever published case of possible MonoMac syndrome with a neurological presentation. The case highlights the rarity and complexity of the diagnosis and the clinical sequelae that ensued with the patient dying of gram-negative septicaemia while receiving intravenous steroid therapy for the spinal cord lesion.


Assuntos
Fator de Transcrição GATA2/genética , Haploinsuficiência/genética , Síndromes de Imunodeficiência/complicações , Infecções por Mycobacterium/complicações , Síndromes Mielodisplásicas/complicações , Doenças da Medula Espinal/complicações , Adulto , Diagnóstico Diferencial , Evolução Fatal , Infecções por Bactérias Gram-Negativas/complicações , Humanos , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/microbiologia , Imagem por Ressonância Magnética/métodos , Masculino , Mutação , Infecções por Mycobacterium/diagnóstico , Infecções por Mycobacterium/microbiologia , Síndromes Mielodisplásicas/microbiologia , Síndromes Mielodisplásicas/patologia , Sepse/complicações , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/tratamento farmacológico , Doenças da Medula Espinal/patologia , Tuberculose Pulmonar/complicações
11.
Vaccine ; 36(24): 3541-3554, 2018 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-29426658

RESUMO

Infectious complications are a major cause of morbidity and mortality in patients with primary or secondary immunodeficiency. Prevention of infectious diseases by vaccines is among the most effective healthcare measures mainly for these subjects. However immunocompromised people vary in their degree of immunosuppression and susceptibility to infection and, therefore, represent a heterogeneous population with regard to immunization. To date there is no well- established evidence for use of vaccines in immunodeficient patients, and indications are not clearly defined even in high-quality reviews and in most of the guidelines prepared to provide recommendations for the active vaccination of immunocompromised hosts. The aim of this document is to issue recommendations based on published literature and the collective experience of the Italian primary immunodeficiency centers, about how and when vaccines can be used in immunocompromised patients, in order to facilitate physician decisions and to ensure the best immune protection with the lowest risk to the health of the patient.


Assuntos
Infecções Bacterianas/prevenção & controle , Vacinas Bacterianas/administração & dosagem , Hospedeiro Imunocomprometido , Guias de Prática Clínica como Assunto , Vacinas Virais/administração & dosagem , Viroses/prevenção & controle , Adulto , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/virologia , Criança , Política de Saúde , Humanos , Esquemas de Imunização , Síndromes de Imunodeficiência/microbiologia , Síndromes de Imunodeficiência/virologia , Itália , Vacinação/métodos , Vacinas de Produtos Inativados , Viroses/imunologia , Viroses/virologia
12.
Eur J Haematol ; 100(3): 315-322, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29240266

RESUMO

BACKGROUND: Posaconazole is a triazole with limited pharmacokinetic information in children. This study assessed the correlation between posaconazole oral solution daily dosage/kg/body weight and trough plasma level. METHODS: A total of 97 hematology-oncology pediatric patients with ≥1 posaconazole plasma concentration level (PPC) assessment in the first 6 weeks after the start of posaconazole treatment were included. RESULTS: Posaconazole was used as prophylaxis in 84 of 97 (87%) patients and as therapy in 13 of 97 (13%). The median daily dose/kg/bw ranged from 10 to 12 mg in the prophylaxis group and 12.5 to 16.5 mg in the therapy group. The median value of PPC for the prophylaxis group was 0.9 and 0.8 µg/mL at the first and second/third determinations, respectively. Posaconazole prophylaxis failed in 4 of 84 patients (5%). The median value of PPC for the therapy group was 1.5 and 1.4 µg/mL at the first/second and the third determination, respectively. Posaconazole-related side effects were reported in 6 patients and all regressed with the suspension of the drug. In the prophylaxis group, the use of proton-pump inhibitors was significantly associated with a lower PPC, P = 0.04. CONCLUSIONS: Posaconazole may be a valuable antifungal agent in children despite the incomplete knowledge of its pharmacokinetic characteristics.


Assuntos
Anemia Aplástica/terapia , Antifúngicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hematológicas/terapia , Síndromes de Imunodeficiência/terapia , Linfo-Histiocitose Hemofagocítica/terapia , Micoses/prevenção & controle , Triazóis/farmacocinética , Administração Oral , Adolescente , Anemia Aplástica/microbiologia , Anemia Aplástica/mortalidade , Anemia Aplástica/patologia , Antifúngicos/sangue , Criança , Pré-Escolar , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Feminino , Neoplasias Hematológicas/microbiologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Síndromes de Imunodeficiência/microbiologia , Síndromes de Imunodeficiência/mortalidade , Síndromes de Imunodeficiência/patologia , Lactente , Linfo-Histiocitose Hemofagocítica/microbiologia , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/patologia , Masculino , Micoses/mortalidade , Indução de Remissão , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo , Triazóis/sangue
13.
Amino Acids ; 50(3-4): 363-372, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29238856

RESUMO

Drug-resistant microorganism infections cause serious disease and can lead to mortality and morbidity. In particular, Staphylococcus aureus induces pyrogenic and toxigenic infections, and drug-resistance occurs rapidly. Multidrug-resistant S. aureus, such as methicillin-resistant S. aureus and methicillin-sensitive S. aureus, can also cause immunodeficiency and immune deficiency syndrome from lipoteichoic acid. However, antimicrobial peptides, such as KW4, have strong antimicrobial activity, low cytotoxicity, and high neutralization activity against endotoxin substances from Gram-negative bacteria. The objective of this study was to use a synthetic KW4 antimicrobial peptide to evaluate the inhibition of drug-resistance development, antimicrobial activity, and neutralizing activity in S. aureus Gram-positive bacteria. The KW4 peptide showed strong antimicrobial activity against drug-resistant S. aureus strains and significantly increased the anti-neutralizing activity of lipoteichoic acid in S. aureus 1630 drug-resistant bacteria. In addition, S. aureus ATCC 29213 did not develop resistance to KW4 as with other antibiotic drugs. These results suggest that the KW4 peptide is an effective antibiotic and anti-neutralizing agent against multidrug-resistant S. aureus strains.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Síndromes de Imunodeficiência/tratamento farmacológico , Inflamação/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Animais , Peptídeos Catiônicos Antimicrobianos/síntese química , Endotoxinas/antagonistas & inibidores , Endotoxinas/biossíntese , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/microbiologia , Síndromes de Imunodeficiência/patologia , Inflamação/induzido quimicamente , Inflamação/imunologia , Inflamação/microbiologia , Lipopolissacarídeos/toxicidade , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Camundongos , Células RAW 264.7 , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Ácidos Teicoicos/toxicidade
14.
J Clin Invest ; 127(12): 4415-4420, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29106381

RESUMO

Primary immunodeficiencies are often monogenic disorders characterized by vulnerability to specific infectious pathogens. Here, we performed whole-exome sequencing of a patient with disseminated Mycobacterium abscessus, Streptococcus viridians bacteremia, and cytomegalovirus (CMV) viremia and identified mutations in 2 genes that regulate distinct IFN pathways. The patient had a homozygous frameshift deletion in IFNGR2, which encodes the signal transducing chain of the IFN-γ receptor, that resulted in minimal protein expression and abolished downstream signaling. The patient also harbored a homozygous deletion in IFNAR1 (IFNAR1*557Gluext*46), which encodes the IFN-α receptor signaling subunit. The IFNAR1*557Gluext*46 resulted in replacement of the stop codon with 46 additional codons at the C-terminus. The level of IFNAR1*557Gluext*46 mutant protein expressed in patient fibroblasts was comparable to levels of WT IFNAR1 in control fibroblasts. IFN-α-induced signaling was impaired in the patient fibroblasts, as evidenced by decreased STAT1/STAT2 phosphorylation, nuclear translocation of STAT1, and expression of IFN-α-stimulated genes critical for CMV immunity. Pretreatment with IFN-α failed to suppress CMV protein expression in patient fibroblasts, whereas expression of WT IFNAR1 restored IFN-α-mediated suppression of CMV. This study identifies a human IFNAR1 mutation and describes a digenic immunodeficiency specific to type I and type II IFNs.


Assuntos
Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/imunologia , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/imunologia , Mutação , Receptor de Interferon alfa e beta , Receptores de Interferon , Bacteriemia/genética , Bacteriemia/imunologia , Bacteriemia/microbiologia , Citomegalovirus/imunologia , Infecções por Citomegalovirus/genética , Infecções por Citomegalovirus/imunologia , Feminino , Fibroblastos/imunologia , Fibroblastos/microbiologia , Fibroblastos/virologia , Doenças Genéticas Inatas/microbiologia , Doenças Genéticas Inatas/virologia , Humanos , Síndromes de Imunodeficiência/microbiologia , Síndromes de Imunodeficiência/virologia , Masculino , Infecções por Micobactéria não Tuberculosa/genética , Infecções por Micobactéria não Tuberculosa/imunologia , Mycobacterium abscessus/imunologia , Fosforilação/genética , Fosforilação/imunologia , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/imunologia , Receptores de Interferon/genética , Receptores de Interferon/imunologia , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/imunologia , Fator de Transcrição STAT2/genética , Fator de Transcrição STAT2/imunologia , Infecções Estreptocócicas/genética , Infecções Estreptocócicas/imunologia , Viremia/genética , Viremia/imunologia , Viremia/virologia , Estreptococos Viridans/imunologia
15.
PLoS One ; 12(8): e0181365, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28796780

RESUMO

Salmonella enterica are a threat to public health. Current vaccines are not fully effective. The ability to grow in infected tissues within phagocytes is required for S. enterica virulence in systemic disease. As the infection progresses the bacteria are exposed to a complex host immune response. Consequently, in order to continue growing in the tissues, S. enterica requires the coordinated regulation of fitness genes. Bacterial gene regulation has so far been investigated largely using exposure to artificial environmental conditions or to in vitro cultured cells, and little information is available on how S. enterica adapts in vivo to sustain cell division and survival. We have studied the transcriptome, proteome and metabolic flux of Salmonella, and the transcriptome of the host during infection of wild type C57BL/6 and immune-deficient gp91-/-phox mice. Our analyses advance the understanding of how S. enterica and the host behaves during infection to a more sophisticated level than has previously been reported.


Assuntos
Proteínas de Bactérias/genética , Proteoma/genética , Salmonelose Animal/genética , Salmonelose Animal/microbiologia , Salmonella typhimurium/genética , Transcriptoma , Animais , Proteínas de Bactérias/análise , Feminino , Deleção de Genes , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteoma/análise , Receptores Imunológicos/análise , Receptores Imunológicos/genética
16.
BMC Res Notes ; 10(1): 177, 2017 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-28476145

RESUMO

BACKGROUND: The Bacillus Calmette-Guérin (BCG) preparations are live-attenuated derivatives of Mycobacterium bovis. These products are used to vaccinate infants at birth, a practice that may result in a disseminated infection in those patients who have an unidentified immunodeficiency. CASE PRESENTATION: Patients who were immunized at birth with BCG and who developed a disseminated infection are reported here to emphasize the importance of taking an extensive medical history before giving the BCG vaccine. Patient 1 has a sibling who had familial hemophagocytic lymphohistiocytosis. Patient 2 has a severe immunodeficiency with profound lymphopenia. Patient 3 has a sibling who had a disseminated BCG infection. Patient 4 has two siblings with an immunodeficiency disorder; one sibling passed away in infancy and one is receiving regular immunoglobulin infusions. Patient 5 has profound lymphopenia and his brother had cytomegalovirus (CMV) pneumonitis and passed away in infancy. CONCLUSIONS: These unfortunate events could have been avoided by compiling the relevant clinical and laboratory information. These cases also underscore the importance of a strict adherence to the BCG vaccine policies. Local and international registries that estimate the birth prevalence of primary immune deficiencies are needed prior to implementing universal BCG vaccination administration.


Assuntos
Vacina BCG/efeitos adversos , Contraindicações de Medicamentos , Síndromes de Imunodeficiência/microbiologia , Tuberculose/microbiologia , Vacinação/efeitos adversos , Criança , Feminino , Humanos , Síndromes de Imunodeficiência/complicações , Lactente , Masculino , Mycobacterium bovis/crescimento & desenvolvimento , Mycobacterium bovis/imunologia , Tuberculose/complicações , Tuberculose/etiologia , Tuberculose/imunologia
18.
PLoS One ; 12(2): e0170354, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28152029

RESUMO

Although serogroup 6 was among the first to be recognized among Streptococcus pneumoniae, several new serotypes were identified since the introduction of pneumococcal conjugate vaccines (PCVs). A decrease of the 6B-2 variant among invasive pneumococcal disease (IPD), but not 6B-1, was noted post conjugate vaccine introduction, underpinned by a decrease of CC273 isolates. Serotype 6C was associated with adult IPD and increased in this age group representing two lineages (CC315 and CC395), while the same lineages expressed other serogroup 6 serotypes in children. Taken together, these findings suggest a potential cross-protection of PCVs against serotype 6C IPD among vaccinated children but not among adults. Serotype 6A became the most important serogroup 6 serotype in children but it decreased in adult IPD. No other serogroup 6 serotypes were detected, so available phenotypic or simple genotypic assays remain adequate for distinguishing serotypes within serogroup 6 isolates.


Assuntos
Proteção Cruzada/imunologia , Vacina Pneumocócica Conjugada Heptavalente/imunologia , Síndromes de Imunodeficiência/epidemiologia , Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/imunologia , Adulto , Antibacterianos/farmacologia , Humanos , Síndromes de Imunodeficiência/microbiologia , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Infecções Pneumocócicas/microbiologia , Portugal/epidemiologia , Sorogrupo , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação , Vacinação
19.
J Antimicrob Chemother ; 71(suppl 2): ii23-ii29, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27880666

RESUMO

Diagnosing invasive aspergillosis (IA) has long been challenging due to the inability to culture the causal Aspergillus agent from blood or other body fluids. This shortcoming has fuelled an interest in non-culture-based diagnostic techniques such as the detection of galactomannan (GM) in blood and bronchoalveolar lavage fluid, the detection of 1,3-ß-d-glucan (BDG) in blood and the detection of Aspergillus DNA by PCR-based techniques. Past decades have witnessed important improvements in our understanding of the strengths and limitations of antigen assays and in the standardization of PCR-based DNA techniques. These assays are now being incorporated into care pathways and diagnostic algorithms; they help us to steward and monitor antifungal therapies and to predict treatment outcomes.


Assuntos
Aspergillus/efeitos dos fármacos , Aspergillus/isolamento & purificação , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Biomarcadores/sangue , Líquido da Lavagem Broncoalveolar/química , DNA Fúngico/sangue , Humanos , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/microbiologia , Aspergilose Pulmonar Invasiva/microbiologia , Mananas/sangue , Reação em Cadeia da Polimerase , beta-Glucanas/sangue
20.
BMC Infect Dis ; 16: 493, 2016 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-27643790

RESUMO

BACKGROUND: Cupriavidus gilardii is an aerobic, Gram-negative, glucose-nonfermenting rod that was first identified in 1999. Because of the difficulty in accurate species identification of C. gilardii, there are few case reports of infection caused by this organism. In previous reports, C. gilardii has been characterized as an organism with low pathogenicity that causes opportunistic infections. CASE PRESENTATION: We encountered a case of pacemaker-associated bloodstream infection caused by C. gilardii in a 90-year old woman without obvious immunodeficiency. We identified the isolates as C. gilardii by sequencing of the 16S rRNA gene. The patient was treated with removal of the lead and administration of antimicrobial agents. Because of the acquisition of antibiotic resistance during antibiotic treatment, the antimicrobial agent was changed during the course of treatment. CONCLUSIONS: To our knowledge, this is the first report of an infection caused by this organism in a patient without obvious immunodeficiency. Although the true pathogenicity of C. gilardii is unclear, the possibility that it exerts pathogenicity not only in persons with immunodeficiency but also in immunocompetent persons is suggested.


Assuntos
Cupriavidus , Infecções por Bactérias Gram-Negativas/microbiologia , Idoso de 80 Anos ou mais , Feminino , Humanos , Síndromes de Imunodeficiência/microbiologia , Marca-Passo Artificial/microbiologia , RNA Ribossômico 16S/genética
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