RESUMO
Mortality from tuberculous meningitis (TBM) remains around 30%, with most deaths occurring within 2 months of starting treatment. Mortality from drug-resistant strains is higher still, making early detection of drug resistance (DR) essential. Targeted next-generation sequencing (tNGS) produces high read depths, allowing the detection of DR-associated alleles with low frequencies. We applied Deeplex Myc-TB-a tNGS assay-to cerebrospinal fluid (CSF) samples from 72 adults with microbiologically confirmed TBM and compared its genomic drug susceptibility predictions to a composite reference standard of phenotypic susceptibility testing (pDST) and whole genome sequencing, as well as to clinical outcomes. Deeplex detected Mycobacterium tuberculosis complex DNA in 24/72 (33.3%) CSF samples and generated full DR reports for 22/24 (91.7%). The read depth generated by Deeplex correlated with semi-quantitative results from MTB/RIF Xpert. Alleles with <20% frequency were seen at canonical loci associated with first-line DR. Disregarding these low-frequency alleles, Deeplex had 100% concordance with the composite reference standard for all drugs except pyrazinamide and streptomycin. Three patients had positive CSF cultures after 30 days of treatment; reference tests and Deeplex identified isoniazid resistance in two, and Deeplex alone identified low-frequency rifampin resistance alleles in one. Five patients died, of whom one had pDST-identified pyrazinamide resistance. tNGS on CSF can rapidly and accurately detect drug-resistant TBM, but its application is limited to those with higher bacterial loads. In those with lower bacterial burdens, alternative approaches need to be developed for both diagnosis and resistance detection.
Assuntos
Mycobacterium tuberculosis , Tuberculose Meníngea , Tuberculose Resistente a Múltiplos Medicamentos , Adulto , Humanos , Tuberculose Meníngea/diagnóstico , Tuberculose Meníngea/tratamento farmacológico , Tuberculose Meníngea/líquido cefalorraquidiano , Mycobacterium tuberculosis/genética , Pirazinamida , Sensibilidade e Especificidade , Rifampina/farmacologia , Rifampina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Líquido Cefalorraquidiano , Testes de Sensibilidade MicrobianaRESUMO
Using various chromatographic separations, six glycoside derivatives (1-6), including one new ent-labdane glucoside named cayratioside (1), were isolated from the methanol extract of Cayratia geniculata stems and leaves. Their structures were elucidated by detailed analysis of the 1D, 2D NMR, and HRESIQTOF mass spectra. The inhibitory effect of 1-6 on LPS-induced NO production in RAW264.7 cells was also evaluated. Among isolated compounds, 1 exhibited moderate activity with an IC50 value of 59.65 ± 1.85 µM.
Assuntos
Glicosídeos , Óxido Nítrico , Folhas de Planta , Glicosídeos/química , Glicosídeos/farmacologia , Glicosídeos/isolamento & purificação , Camundongos , Animais , Estrutura Molecular , Células RAW 264.7 , Óxido Nítrico/biossíntese , Óxido Nítrico/antagonistas & inibidores , Folhas de Planta/química , Lipopolissacarídeos/farmacologia , Caules de Planta/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificaçãoRESUMO
BACKGROUND: In people with HIV (PWH), the WHO-recommended tuberculosis four-symptom screen (W4SS) targeting those who need molecular rapid test may be suboptimal. We assessed the performance of different tuberculosis screening approaches in severely immunosuppressed PWH enrolled in the guided-treatment group of the STATIS trial (NCT02057796). METHODS: Ambulatory PWH with no overt evidence of tuberculosis and CD4 cell count <100/µL were screened for tuberculosis prior to antiretroviral therapy (ART) initiation with W4SS, chest X-ray, urine lipoarabinomannan (LAM) test and sputum Xpert MTB/RIF® (Xpert). Correctly and wrongly identified cases by screening approaches were assessed overall and by CD4 count threshold (≤50 and 51-99 cells/µL). RESULTS: Of 525 enrolled participants (median CD4 cell count: 28/µL), 48 (9.9%) were diagnosed with tuberculosis at enrollment. Among participants with a negative W4SS, 16% had either a positive Xpert, a chest X-ray suggestive of tuberculosis or a positive urine LAM test. The combination of sputum Xpert and urine LAM test was associated with the highest proportion of participants correctly identified as tuberculosis (95.8%) and non-tuberculosis cases (95.4%), with proportions equally high among participants with CD4 counts above or below 50 cells/µL. Restricting the use of sputum Xpert, urine LAM test or chest X-ray to participants with a positive W4SS reduced the proportion of wrongly and correctly identified cases. CONCLUSIONS: There is a clear benefit to perform both sputum Xpert and urine LAM tests as tuberculosis screening in all severely immunosuppressed PWH prior to ART initiation, and not only in those with a positive W4SS. CLINICAL TRIALS REGISTRATION: NCT02057796.
RESUMO
Multiple Input Multiple Output Orthogonal Frequency Division Multiplexing (MIMO OFDM) is a key technology for wireless communication systems. However, because of the problem of a high peak-to-average power ratio (PAPR), OFDM symbols can be distorted at the MIMO OFDM transmitter. It degrades the signal detection and channel estimation performance at the MIMO OFDM receiver. In this paper, three deep neural network (DNN) models are proposed to solve the problem of non-linear distortions introduced by the power amplifier (PA) of the transmitters and replace the conventional digital signal processing (DSP) modules at the receivers in 2 × 2 MIMO OFDM and 4 × 4 MIMO OFDM systems. Proposed model type I uses the DNN model to de-map the signals at the receiver. Proposed model type II uses the DNN model to learn and filter out the channel noises at the receiver. Proposed model type III uses the DNN model to de-map and detect the signals at the receiver. All three model types attempt to solve the non-linear problem. The robust bit error rate (BER) performances of the proposed receivers are achieved through the software and hardware implementation results. In addition, we have also implemented appropriate hardware architectures for the proposed DNN models using special techniques, such as quantization and pipeline to check the feasibility in practice, which recent studies have not done. Our hardware architectures are successfully designed and implemented on the Virtex 7 vc709 FPGA board.
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Five asterosaponins (1-5), including one new compound named protonodososide (1), were isolated from the methanol extract of the starfish Protoreaster nodosus, after subjecting to various chromatographic separations. The structural elucidation was confirmed by careful analysis of the 1D, 2D NMR, and HR ESI QTOF mass spectra. The cytotoxicity of isolated compounds was evaluated on five human cancer cell lines including HepG2, KB, MCF7, LNCaP, and SK-Mel2.
Assuntos
Antineoplásicos , Estrelas-do-Mar , Animais , Humanos , Estrelas-do-Mar/química , Espectroscopia de Ressonância Magnética , Linhagem Celular Tumoral , Espectrometria de Massas por Ionização por Electrospray , Antineoplásicos/química , Estrutura MolecularRESUMO
Three new sulfated naphthopyrone derivatives namely delicapyrons F-H (1-3) and two new sulfated anthraquinone derivatives namely delicaquinons A (4) and B (5), together with 6-methoxycomaparvin-5-methylether-8-O-sodium sulfate (6), 6-methoxycomaparvin-8-O-sodium sulfate (7), comaparvin-8-O-sodium sulfate (8), and 3-propyl-1,6,8-trihydroxy-9,10-anthraquinone-6-O-sodium sulfate (9) were isolated from the Vietnamese crinoid Comanthus delicata. Their chemical structures were elucidated by extensive analysis of the one dimensional (1D) and 2D-NMR, high resolution electrospray ionization quadrupole time-of-flight (HR-ESI-QTOF) mass spectra as well as calculation of optical rotation. In addition, significant cytotoxicity was observed for 6 against LNCaP (prostate cancer) cell line with IC50 value of 20.29 ± 2.43 µM, whereas moderate or weak cytotoxic effects were observed for 1-3 and 5-8 on SK-Mel-2 (melanoma) cell line and 7 and 8 against LNCaP cell line, with IC50 values ranging from 49.96 ± 1.74 to 76.92 ± 5.85 µM.
Assuntos
Antineoplásicos , Neoplasias , Animais , Antraquinonas/química , Antraquinonas/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Povo Asiático , Equinodermos/química , HumanosRESUMO
Antimicrobials are a key group of therapeutic agents. Given the animal/human population density and high antimicrobial consumption rate in Southeast Asia, the region is a focal area for monitoring antimicrobial resistance (AMR). Hypothesizing that the gastrointestinal tract of healthy individuals in Vietnam is a major source of AMR genes that may be transferred to pathogens, we performed shotgun metagenomic sequencing on fecal samples from 42 healthy Vietnamese people (21 children and 21 adults). We compared their microbiome profiles by age group and determined the composition of AMR genes. An analysis of the taxonomic profiles in the gut microbiome showed a clear differentiation by age, with young children (age <2 years) exhibiting a unique structure in comparison to adults and older children. We identified a total of 132 unique AMR genes, with macrolide, lincosamide, and streptogramin class resistance genes (ermB and lnuC) and tetracycline resistance genes being almost ubiquitous across the study population. Notably, samples from younger children were significantly associated with a greater number of AMR genes than other age groups, including key signature genes associated with AMR pathogens (eg, blaCTX-M, mphA). Our data suggest that the gut microbiome of those living in Vietnam, particularly young children, is a substantial reservoir of AMR genes, which can be transferred to circulating enteric pathogens. Our data support the generation of longitudinal cohort studies of those living in urban and rural areas of developing countries to understand the behavior of these AMR reservoirs and their role in generating multidrug-resistant and extensively drug-resistant pathogens.
Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Fezes/microbiologia , Microbioma Gastrointestinal , Metagenômica , Adolescente , Adulto , Idoso , Animais , Povo Asiático , Criança , Pré-Escolar , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , VietnãRESUMO
Introduction: Telepharmacy, the application of information and communication technologies in healthcare services, has been adopted in many countries to provide patients with pharmaceutical care. However, it has yet to be widely used in Vietnam. This study was conducted to assess the current status of use and the factors associated with the willingness to use telepharmacy of pharmacists in Vietnam. Methods: A descriptive cross-sectional study was conducted from February to July 2021; 414 pharmacists were recruited to fill in an online survey. Results: Overall, 86.7% of participants have used telepharmacy application and 87.2% of them were willing to apply telepharmacy in pharmacy practice. According to our multivariate analysis, the level of readiness was associated with positive attitude (odds ratio [OR] = 4.67; 95% confidence interval [CI]: 2.26-9.66), and a good behavior (OR = 11.34; 95% CI: 3.84-33.45). Discussion: Developing a telepharmacy system with appropriate features is essential to meet the requirements of pharmacy practice amid the spread of the COVID-19 pandemic.
RESUMO
We investigated the value of susceptibility testing in predicting response in AIDS-associated cryptococcal meningitis using clinical isolates from a randomized controlled trial of antifungal treatment (amphotericin monotherapy, amphotericin with flucytosine, or amphotericin with fluconazole). We found no correlation between antifungal susceptibility and either early or late survival, or fungal clearance.
Assuntos
Síndrome da Imunodeficiência Adquirida , Meningite Criptocócica , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Flucitosina/uso terapêutico , Humanos , Meningite Criptocócica/tratamento farmacológicoRESUMO
Two new megastigmane glucosides namely trewiosides A (1) and B (2), along with 20α-hydroxypregn-4-en-3-one ß-D-glucopyranoside (3), sugeroside (4), and schizandriside (5) were isolated from the branches and leaves of Alchornea trewioides. The structure elucidation was confirmed by extensive analysis of the one and two dimensional (1 and 2D) NMR, electronic circular dichroism (ECD) as well as high resolution electrospray ionization quadrupole time-of-flight (HR-ESI-QTOF) mass spectra. Noteworthily, the isolation of compounds 1 and 2 represents the second finding of megastigmane derivatives with a methoxycarbonyl group at C-5 to date. In addition, compound 3 showed weak cytotoxicity against three human cancer cell lines as A549 (lung carcinoma), HepG2 (hepatocarcinoma), and MCF7 (breast carcinoma). Besides, compounds 2 and 3 exhibited moderate inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells. Whereas, the remaining compounds 1, 4 and 5 showed weak inhibitory activity.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Euphorbiaceae/química , Óxido Nítrico/antagonistas & inibidores , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Teoria da Densidade Funcional , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Óxido Nítrico/biossíntese , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células RAW 264.7RESUMO
In our search for cytotoxic constituents from Vietnamese plants, the methanolic extract of Isotrema tadungense was found to exhibit significant cytotoxic effect. Subsequent phytochemical investigation of ethyl acetate fractions of this plant led to isolation of 11 compounds including one new arylbenzofuran rhamnoside namely aristolochiaside (1), two aristololactams (2 and 3), three lignanamides (4-6) and five phenolic amides (7-11). Their structures were elucidated by 1 D and 2 D NMR and HR-QTOF-MS experiments. Among the isolated compounds, aristolochiaside (1), aristolactam AIIIa (2) and N-trans-sinapoyltyramine (10) exhibited strong and selective cytotoxicity on the HeLa human cancer cell line with IC50 values of 7.59 ± 1.03, 8.51 ± 1.73 and 9.77 ± 1.25 µM, respectively.[Formula: see text].
Assuntos
Antineoplásicos , Amidas , Antineoplásicos/farmacologia , Células HeLa , Humanos , Estrutura Molecular , Extratos VegetaisRESUMO
BACKGROUND: Approximately 6% of children hospitalized with severe falciparum malaria in Africa are also bacteremic. It is therefore recommended that all children with severe malaria should receive broad-spectrum antibiotics in addition to parenteral artesunate. Empirical antibiotics are not recommended currently for adults with severe malaria. METHODS: Blood cultures were performed on sequential prospectively studied adult patients with strictly defined severe falciparum malaria admitted to a single referral center in Vietnam between 1991 and 2003. RESULTS: In 845 Vietnamese adults with severe falciparum malaria admission blood cultures were positive in 9 (1.07%: 95% confidence interval [CI], .37-1.76%); Staphylococcus aureus in 2, Streptococcus pyogenes in 1, Salmonella Typhi in 3, Non-typhoid Salmonella in 1, Klebsiella pneumoniae in 1, and Haemophilus influenzae type b in 1. Bacteremic patients presented usually with a combination of jaundice, acute renal failure, and high malaria parasitemia. Four bacteremic patients died compared with 108 (12.9%) of 836 nonbacteremic severe malaria patients (risk ratio, 3.44; 95% CI, 1.62-7.29). In patients withâ >20% parasitemia the prevalence of concomitant bacteremia was 5.2% (4/76; 95% CI, .2-10.3%) compared with 0.65% (5/769; 0.08-1.2%) in patients withâ <20% parasitemia, a risk ratio of 8.1 (2.2-29.5). CONCLUSIONS: In contrast to children, the prevalence of concomitant bacteremia in adults with severe malaria is low. Administration of empirical antibiotics, in addition to artesunate, is warranted in the small subgroup of patients with very high parasitemias, emphasizing the importance of quantitative blood smear microscopy assessment, but it is not indicated in most adults with severe falciparum malaria.
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Antimaláricos , Artemisininas , Bacteriemia , Malária Falciparum , Malária , Adulto , África , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Bacteriemia/complicações , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Criança , Humanos , Malária/tratamento farmacológico , Malária Falciparum/complicações , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Plasmodium falciparum , Vietnã/epidemiologiaRESUMO
Nontyphoidal Salmonella (NTS) are among the most common etiological agents of diarrheal diseases worldwide and have become the most commonly detected bacterial pathogen in children hospitalized with diarrhea in Vietnam. Aiming to better understand the epidemiology, serovar distribution, antimicrobial resistance (AMR), and clinical manifestation of NTS gastroenteritis in Vietnam, we conducted a clinical genomics investigation of NTS isolated from diarrheal children admitted to one of three tertiary hospitals in Ho Chi Minh City. Between May 2014 and April 2016, 3,166 children hospitalized with dysentery were recruited into the study; 478 (â¼15%) children were found to be infected with NTS by stool culture. Molecular serotyping of the 450 generated genomes identified a diverse collection of serogroups (B, C1, C2 to C3, D1, E1, G, I, K, N, O, and Q); however, Salmonella enterica serovar Typhimurium was the most predominant serovar, accounting for 41.8% (188/450) of NTS isolates. We observed a high prevalence of AMR to first-line treatments recommended by WHO, and more than half (53.8%; 242/450) of NTS isolates were multidrug resistant (MDR; resistant to ≥3 antimicrobial classes). AMR gene detection positively correlated with phenotypic AMR testing, and resistance to empirical antimicrobials was associated with a significantly longer hospitalization (0.91 days; P = 0.04). Our work shows that genome sequencing is a powerful epidemiological tool to characterize the serovar diversity and AMR profiles in NTS. We propose a revaluation of empirical antimicrobials for dysenteric diarrhea and endorse the use of whole-genome sequencing for sustained surveillance of NTS internationally.
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Anti-Infecciosos , Gastroenterite , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Criança , Criança Hospitalizada , Farmacorresistência Bacteriana , Farmacorresistência Bacteriana Múltipla/genética , Gastroenterite/epidemiologia , Genômica , Humanos , Testes de Sensibilidade Microbiana , Sorotipagem , Vietnã/epidemiologiaRESUMO
BACKGROUND: Diarrhoeagenic Escherichia coli (DEC) infections are common in children in low-middle income countries (LMICs). However, detecting the various DEC pathotypes is complex as they cannot be differentiated by classical microbiology. We developed four multiplex real-time PCR assays were to detect virulence markers of six DEC pathotypes; specificity was tested using DEC controls and other enteric pathogens. PCR amplicons from the six E. coli pathotypes were purified and amplified to be used to optimize PCR reactions and to calculate reproducibility. After validation, these assays were applied to clinical samples from healthy and diarrhoeal Vietnamese children and associated with clinical data. RESULTS: The multiplex real-time PCRs were found to be reproducible, and specific. At least one DEC variant was detected in 34.7% (978/2815) of the faecal samples from diarrhoeal children; EAEC, EIEC and atypical EPEC were most frequent Notably, 41.2% (205/498) of samples from non-diarrhoeal children was positive with a DEC pathotype. In this population, only EIEC, which was detected in 34.3% (99/289) of diarrhoeal samples vs. 0.8% (4/498) non-diarrhoeal samples (p < 0.001), was significantly associated with diarrhoea. Multiplex real-time PCR when applied to clinical samples is an efficient and high-throughput approach to DEC pathotypes. CONCLUSIONS: This approach revealed high carriage rates of DEC pathotypes among Vietnamese children. We describe a novel diagnostic approach for DEC, which provides baseline data for future surveillance studies assessing DEC burden in LMICs.
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Diarreia/microbiologia , Escherichia coli Enteropatogênica/classificação , Infecções por Escherichia coli/diagnóstico , Infecções por Escherichia coli/epidemiologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adolescente , Criança , Pré-Escolar , Diarreia/epidemiologia , Escherichia coli Enteropatogênica/genética , Escherichia coli Enteropatogênica/isolamento & purificação , Escherichia coli Enteropatogênica/patogenicidade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase Multiplex , Prevalência , Sensibilidade e Especificidade , Vietnã/epidemiologia , Fatores de Virulência de BordetellaRESUMO
Chemical investigation of the aerial parts of Andrographis paniculata resulted in isolation of nine compounds, including a new ent-labdane diterpenoid, andrographic acid methyl ester (1), a new chalcone glucoside, pashanone glucoside (5), and seven known metabolites, andrograpanin (2), andrographolide (3), andropanolide (4), andrographidine A (6), andrographidine F (7), 6-epi-8-O-acetyl-harpagide (8), and curvifloruside F (9). Their chemical structures were elucidated based on comprehensive analyses of the spectroscopic data, including NMR and MS. Among the isolated compounds, andropanolide exerted cytotoxicity toward LNCaP, HepG2, KB, MCF7, and SK-Mel2 carcinoma cells, with IC50 values ranging from 31.8 to 45.9 µM. In addition, andropanolide significantly inhibited the overproduction of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, with an IC50 value of 13.4 µM.
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Andrographis/química , Diterpenos/química , Flavonoides/química , Andrographis/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Humanos , Lipopolissacarídeos/toxicidade , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Conformação Molecular , Óxido Nítrico/metabolismo , Componentes Aéreos da Planta/química , Componentes Aéreos da Planta/metabolismo , Células RAW 264.7RESUMO
Background: Nontyphoidal Salmonella (NTS) organisms are a major cause of gastroenteritis and bacteremia, but little is known about maternally acquired immunity and natural exposure in infant populations residing in areas where NTS disease is highly endemic. Methods: We recruited 503 pregnant mothers and their infants (following delivery) from urban areas in Vietnam and followed infants until they were 1 year old. Exposure to the dominant NTS serovars, Salmonella enterica serovars Typhimurium and Enteritidis, were assessed using lipopolysaccharide (LPS) O antigen-specific antibodies. Antibody dynamics, the role of maternally acquired antibodies, and NTS seroincidence rates were modeled using multivariate linear risk factor models and generalized additive mixed-effect models. Results: Transplacental transfer of NTS LPS-specific maternal antibodies to infants was highly efficient. Waning of transplacentally acquired NTS LPS-specific antibodies at 4 months of age left infants susceptible to Salmonella organisms, after which they began to seroconvert. High seroincidences of S. Typhimurium and S. Enteritidis LPS were observed, and infants born with higher anti-LPS titers had greater plasma bactericidal activity and longer protection from seroconversion. Conclusions: Although Vietnamese infants have extensive exposure to NTS, maternally acquired antibodies appear to play a protective role against NTS infections during early infancy. These findings suggest that prenatal immunization may be an appropriate strategy to protect vulnerable infants from NTS disease.
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Anticorpos Antibacterianos/imunologia , Imunidade Materno-Adquirida/imunologia , Imunidade , Infecções por Salmonella/imunologia , Adulto , Anticorpos Antibacterianos/sangue , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Lipopolissacarídeos/imunologia , Masculino , Análise Multivariada , Antígenos O , Fatores de Risco , Salmonella enteritidis , Salmonella typhimurium , Estudos Soroepidemiológicos , Sorogrupo , VietnãRESUMO
Background: Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis. We developed and validated prognostic models for 9-month mortality in adults with TBM, with or without human immunodeficiency virus (HIV) infection. Methods: We included 1699 subjects from 4 randomized clinical trials and 1 prospective observational study conducted at 2 major referral hospitals in Southern Vietnam from 2001-2015. Modeling was based on multivariable Cox proportional hazards regression. The final prognostic models were validated internally and temporally and were displayed using nomograms and a Web-based app (https://thaole.shinyapps.io/tbmapp/). Results: 951 HIV-uninfected and 748 HIV-infected subjects with TBM were included; 219 of 951 (23.0%) and 384 of 748 (51.3%) died during 9-month follow-up. Common predictors for increased mortality in both populations were higher Medical Research Council (MRC) disease severity grade and lower cerebrospinal fluid lymphocyte cell count. In HIV-uninfected subjects, older age, previous tuberculosis, not receiving adjunctive dexamethasone, and focal neurological signs were additional risk factors; in HIV-infected subjects, lower weight, lower peripheral blood CD4 cell count, and abnormal plasma sodium were additional risk factors. The areas under the receiver operating characteristic curves (AUCs) for the final prognostic models were 0.77 (HIV-uninfected population) and 0.78 (HIV-infected population), demonstrating better discrimination than the MRC grade (AUC, 0.66 and 0.70) or Glasgow Coma Scale score (AUC, 0.68 and 0.71) alone. Conclusions: The developed models showed good performance and could be used in clinical practice to assist physicians in identifying patients with TBM at high risk of death and with increased need of supportive care.
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Coinfecção/mortalidade , Infecções por HIV/complicações , Modelos Teóricos , Tuberculose Meníngea/mortalidade , Adulto , Fatores Etários , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , Infecções por HIV/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Nomogramas , Estudos Observacionais como Assunto , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Fatores de Tempo , VietnãRESUMO
Background: Pediatric diarrheal disease presents a major public health burden in low- to middle-income countries. The clinical benefits of empirical antimicrobial treatment for diarrhea are unclear in settings that lack reliable diagnostics and have high antimicrobial resistance (AMR). Methods: We conducted a prospective multicenter cross-sectional study of pediatric patients hospitalized with diarrhea containing blood and/or mucus in Ho Chi Minh City, Vietnam. Clinical parameters, including disease outcome and treatment, were measured. Shigella, nontyphoidal Salmonella (NTS), and Campylobacter were isolated from fecal samples, and their antimicrobial susceptibility profiles were determined. Statistical analyses, comprising log-rank tests and accelerated failure time models, were performed to assess the effect of antimicrobials on disease outcome. Results: Among 3166 recruited participants (median age 10 months; interquartile range, 6.5-16.7 months), one-third (1096 of 3166) had bloody diarrhea, and 25% (793 of 3166) were culture positive for Shigella, NTS, or Campylobacter. More than 85% of patients (2697 of 3166) were treated with antimicrobials; fluoroquinolones were the most commonly administered antimicrobials. AMR was highly prevalent among the isolated bacteria, including resistance against fluoroquinolones and third-generation cephalosporins. Antimicrobial treatment and multidrug resistance status of the infecting pathogens were found to have no significant effect on outcome. Antimicrobial treatment was significantly associated with an increase in the duration of hospitalization with particular groups of diarrheal diseases. Conclusions: In a setting with high antimicrobial usage and high AMR, our results imply a lack of clinical benefit for treating diarrhea with antimicrobials; adequately powered randomized controlled trials are required to assess the role of antimicrobials for diarrhea.
Assuntos
Antibacterianos/uso terapêutico , Diarreia/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla , Fezes/microbiologia , Adolescente , Campylobacter/efeitos dos fármacos , Criança , Pré-Escolar , Estudos Transversais , Diarreia/microbiologia , Feminino , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Prevalência , Estudos Prospectivos , Salmonella/efeitos dos fármacos , Shigella/efeitos dos fármacos , Resultado do Tratamento , VietnãRESUMO
BACKGROUND: Enteroviruses are the most common causative agents of human illness. Enteroviruses have been associated with regional and global epidemics, recently, including with severe disease (Enterovirus A71 and D68), and are of interest as emerging viruses. Here, we typed Enterovirus A-D (EV) from central nervous system (CNS) and respiratory infections in Viet Nam. METHODS: Data and specimens from prospective observational clinical studies conducted between 1997 and 2010 were used. Species and serotypes were determined using type-specific RT-PCR and viral protein 1 or 4 (VP1, VP4) sequencing. RESULTS: Samples from patients with CNS infection (51 children - 10 CSF and 41 respiratory/rectal swabs) and 28 adults (28 CSF) and respiratory infection (124 children - 124 respiratory swabs) were analysed. Twenty-six different serotypes of the four Enterovirus species (A-D) were identified, including EV-A71 and EV-D68. Enterovirus B was associated with viral meningitis in children and adults. Hand, foot and mouth disease associated Enteroviruses A (EV-A71 and Coxsackievirus [CV] A10) were detected in children with encephalitis. Diverse serotypes of all four Enterovirus species were found in respiratory samples, including 2 polio-vaccine viruses, but also 8 CV-A24 and 8 EV-D68. With the exception of EV-D68, the relevance of these viruses in respiratory infection remains unknown. CONCLUSION: We describe the diverse spectrum of enteroviruses from patients with CNS and respiratory infections in Viet Nam between 1997 and 2010. These data confirm the global circulation of Enterovirus genera and their associations and are important for clinical diagnostics, patient management, and outbreak response.
Assuntos
Infecções do Sistema Nervoso Central/epidemiologia , Infecções do Sistema Nervoso Central/virologia , Infecções por Enterovirus/epidemiologia , Infecções por Enterovirus/virologia , Enterovirus/classificação , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Adolescente , Adulto , Infecções do Sistema Nervoso Central/diagnóstico , Infecções do Sistema Nervoso Central/história , Criança , Pré-Escolar , Enterovirus/genética , Enterovirus/isolamento & purificação , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/história , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , História do Século XX , História do Século XXI , Humanos , Lactente , Masculino , Filogenia , Vigilância da População , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/história , Estações do Ano , Análise de Sequência de DNA , Sorogrupo , Vietnã/epidemiologia , Adulto JovemRESUMO
Seven anthraquinones including two new compounds namely capillasterquinones A and B (1 and 2) and one new butenolide namely capillasterolide (8) were isolated and structurally elucidated from the crinoid Capillaster multiradiatus. The inhibitory effect of compounds 1-8 on lipopolysaccharide (LPS)-induced nitric oxide (NO) production as well as inhibition of 1 on expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) proteins in RAW264.7 cells were also evaluated. As the obtained results, capillasterquinone A (1) showed strong NO production inhibitory activity with an IC50 of 5.89±0.11 µM. In addition, compound 1 reduced the LPS-induced iNOS and COX-2 expressions in a dose-dependent manner.