RESUMO
A point-of-care (POC) device is reported for highly sensitive and selective detection of Plasmodium falciparum lactate dehydrogenase (Pf-LDH), a biomarker of malaria infection, based on a single-step magneto-immunoassay, a single-use microfluidic paper device and a customized hand-held fluorescence reader. The single-step magneto-immunoassay consists in a single 5-min incubation of immuno-modified magnetic particles (c-MAb-MPs), biotinylated detection antibody (bd-MAb), and an enzymatic signal amplifier (Poly-HRP). After on-chip MP concentration and washing, signal generation is achieved by adding a fluorescent enzymatic substrate (QuantaRed). Fluorescence signal is measured using a low-cost customized, portable, and sensible fluorescent detector. The POC affords quantitative Pf-LDH detection in <20 min, with a detection limit of 0.92 ng mL-1 (equivalent to 4.6 parasites µL-1). Furthermore, Pf-LDH quantitation in clinical samples correlates with that provided by the reference ELISA, is more sensitive than a commercial rapid diagnostic test (RDT) and entails little user intervention. These results show that fluorescent paper-based microfluidic devices can be exploited to simplify magneto-immunoassay handling, taking this type of test closer to the requirements of POC testing.
Assuntos
Técnicas Biossensoriais , Malária Falciparum , Malária , Humanos , Imunoensaio , L-Lactato Desidrogenase , Dispositivos Lab-On-A-Chip , Malária/diagnóstico , Malária Falciparum/diagnóstico , Plasmodium falciparumRESUMO
Gonorrhoea infections are frequently diagnosed at extragenital locations in asymptomatic individuals and are historically related to poor recovery in culture, which hinders antimicrobial susceptibility testing. The aim of this study was to evaluate recovery rates of Neisseria gonorrhoeae by culture among asymptomatic individuals who tested positive by nucleic acid amplification tests between 2018 and 2019 in Barcelona (Spain). In total, 10 396 individuals were tested for N. gonorrhoeae on first-void urine, rectal, pharyngeal and/or vaginal swabs depending on sexual behaviour. Overall infection prevalence was 5·5% (95% confidence interval [CI] 5·0-5·9). Seven hundred and ten samples were positive corresponding to 567 individuals. The most common site of infection was the pharynx (71·3%), followed by rectum (23·1%) and genitals (4·7%) (P < 0·0001). The N. gonorrhoeae recovery rate in culture, time from positive screening to culture specimen and inoculation delay were calculated. Recovery rate was 21·7% in pharynx, 66·9% in rectum and 37·0% in genitals (25·0% vagina, 71·4% urethra) (P < 0·0001). Median culture collection time was 1 [0; 3] days, and median inoculation delay was 5·01 [4·99-7·99] h, with no impact on N. gonorrhoeae recovery, P = 0·8367 and P = 0·7670, respectively. Despite efforts towards optimizing pre-analytical conditions, the N. gonorrhoeae recovery rate in asymptomatic individuals is unacceptably low (especially for pharynx), representing a problem for monitoring antimicrobial-resistant infections.
Assuntos
Gonorreia , Neisseria gonorrhoeae , Feminino , Humanos , Neisseria gonorrhoeae/genética , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Gonorreia/prevenção & controle , Técnicas de Amplificação de Ácido Nucleico , Faringe , RetoRESUMO
BACKGROUND: Chagas disease (CD) continues to be a neglected infectious disease with one of the largest burdens globally. Despite the modest cure rates in adult chronic patients and its safety profile, benznidazole (BNZ) is still the drug of choice. Its current recommended dose is based on nonrandomized studies, and efficacy and safety of the optimal dose of BNZ have been scarcely analyzed in clinical trials. METHODS/DESIGN: MULTIBENZ is a phase II, randomized, noninferiority, double-blind, multicenter international clinical trial. A total of 240 patients with Trypanosoma CD in the chronic phase will be recruited in four different countries (Argentina, Brazil, Colombia, and Spain). Patients will be randomized to receive BNZ 150 mg/day for 60 days, 400 mg/day for 15 days, or 300 mg/day for 60 days (comparator arm). The primary outcome is the efficacy of three different BNZ therapeutic schemes in terms of dose and duration. Efficacy will be assessed according to the proportion of patients with sustained parasitic load suppression in peripheral blood measured by polymerase chain reaction. The secondary outcomes are related to pharmacokinetics and drug tolerability. The follow-up will be 12 months from randomization to end of study participation. Recruitment was started in April 2018. CONCLUSION: This is a clinical trial conducted for the assessment of different dose schemes of BNZ compared with the standard treatment regimen for the treatment of CD in the chronic phase. MULTIBENZ may help to clarify which is the most adequate BNZ regimen in terms of efficacy and safety, predicated on sustained parasitic load suppression in peripheral blood. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03191162. Registered on 19 June 2017.
Assuntos
Doença de Chagas/tratamento farmacológico , Doenças Negligenciadas/parasitologia , Nitroimidazóis/uso terapêutico , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi/isolamento & purificação , Adulto , Assistência ao Convalescente , Argentina/epidemiologia , Brasil/epidemiologia , Estudos de Casos e Controles , Doença de Chagas/parasitologia , Doença Crônica , Colômbia/epidemiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Nitroimidazóis/farmacocinética , Carga Parasitária/estatística & dados numéricos , Segurança , Espanha/epidemiologia , Resultado do Tratamento , Tripanossomicidas/farmacocinética , Trypanosoma cruzi/genéticaAssuntos
Esquistossomose/diagnóstico , Adolescente , Animais , Anti-Helmínticos/administração & dosagem , Criança , Emigrantes e Imigrantes , Feminino , Humanos , Masculino , Praziquantel/administração & dosagem , Estudos Retrospectivos , Schistosoma/isolamento & purificação , Esquistossomose/tratamento farmacológico , Espanha , ViagemRESUMO
OBJECTIVES: The aim was to describe pregnancy outcomes after Zika virus (ZIKV) infection in a non-endemic region. METHODS: According to the Spanish protocol issued after the ZIKV outbreak in Brazil in 2015, all pregnant women who had travelled to high-burden countries were screened for ZIKV. Serological and molecular tests were used to identify ZIKV-infected pregnant women. They were classified as confirmed ZIKV infection when reverse transcription (RT) PCR tested positive, or probable ZIKV infection when ZIKV immunoglobulin M and/or immunoglobulin G and ZIKV plaque reduction neutralization tests were positive. Women found positive using molecular or serological tests were prospectively followed-up with ultrasound scans and neurosonograms on a monthly basis until delivery; magnetic resonance imaging and amniotic fluid testing were performed after signed informed consent. Samples of placenta, and fetal and neonatal tissues were obtained. RESULTS: Seventy-two pregnant women tested positive for ZIKV infection: ten were confirmed by RT-PCR, and 62 were probable cases based on serological tests. The prevalence of adverse perinatal outcomes was 33.3% (three out of nine, 95% CI 12.1-64.6%): two cases of congenital ZIKV syndrome (CZS) and one miscarriage, all born to women infected in the first trimester of gestation. All ZIKV-confirmed women had persistent viraemias beyond 2 weeks (median 61.50 days; IQR 35.50-80.75). Amniotic fluid testing was only positive in the two fetuses with anomalies. CONCLUSION: The prevalence of perinatal adverse outcomes for women with ZIKV-confirmed infection was 33.3%. Amniocentesis for ZIKV RT-PCR is recommended when fetal abnormalities are found. Intensive prenatal and postnatal follow-up of ZIKV-infected pregnancies is advised in confirmed cases.
Assuntos
Resultado da Gravidez , Infecção por Zika virus/complicações , Zika virus/isolamento & purificação , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Brasil , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Gravidez , Estudos Prospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ultrassonografia , Adulto Jovem , Infecção por Zika virus/diagnósticoRESUMO
There is little published data on benznidazole dosing, or levels in cerebrospinal fluid. In this report, we describe the clinical course of an immunosuppressed patient with Chagas central nervous system involvement. He was treated successfully with larger benznidazole doses than are recommended, in order to reach therapeutically effective concentrations in the brain.
Assuntos
Encéfalo/metabolismo , Doença de Chagas/imunologia , Imunossupressores/administração & dosagem , Transplante de Rim , Nitroimidazóis/administração & dosagem , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Nitroimidazóis/farmacocinéticaRESUMO
We describe a case of a pregnant woman with Zika virus (ZIKV) infection and a foetus with severe brain malformations. ZIKV tested positive in amniotic fluid at 19 weeks but was negative at delivery. The newborn did not meet the case definition of congenital ZIKV syndrome because neither ZIKV RNA nor IgM antibodies were detected; however, prenatal brain lesions were confirmed after birth (Graphical Abstract).
Assuntos
Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/etiologia , Malformações do Sistema Nervoso/diagnóstico , Malformações do Sistema Nervoso/etiologia , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/complicações , Infecção por Zika virus/virologia , Zika virus , Adulto , Biomarcadores , Encéfalo/anormalidades , Feminino , Genes Virais , Humanos , Recém-Nascido , Fenótipo , Filogenia , Reação em Cadeia da Polimerase , Gravidez , Diagnóstico Pré-Natal , Zika virus/classificação , Zika virus/genéticaRESUMO
In this study we attempt to assess the utility of a simplified step-wise diagnostic algorithm to determinate the aetiology of encephalitis in daily clinical practice and to describe the main causes in our setting. This was a prospective cohort study of all consecutive cases of encephalitis in adult patients diagnosed between January 2010 and March 2015 at the University Hospital Vall d'Hebron in Barcelona, Spain. The aetiological study was carried out following the proposed step-wise algorithm. The proportion of aetiological diagnoses achieved in each step was analysed. Data from 97 patients with encephalitis were assessed. Following a simplified step-wise algorithm, a definite diagnosis was made in the first step in 53 patients (55 %) and in 12 additional cases (12 %) in the second step. Overall, a definite or probable aetiological diagnosis was achieved in 78 % of the cases. Herpes virus, L. monocytogenes and M. tuberculosis were the leading causative agents demonstrated, whereas less frequent aetiologies were observed, mainly in immunosuppressed patients. The overall related mortality was 13.4 %. According to our experience, the leading and treatable causes of encephalitis can be identified in a first diagnostic step with limited microbiological studies. L. monocytogenes treatment should be considered on arrival in some patients. Additional diagnostic effort should be made in immunosuppressed patients.
Assuntos
Algoritmos , Técnicas de Laboratório Clínico/métodos , Testes Diagnósticos de Rotina/métodos , Encefalite Infecciosa/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha , Adulto JovemRESUMO
According to the WHO, chronic Chagas disease (CD) diagnosis is based on two serological techniques. To establish a definitive diagnosis, the results must be concordant. In cases of discordances, the WHO proposes repeating serology in a new sample, and if results remain inconclusive, a confirmatory test should be performed. This study, conducted at two Tropical Medicine Units in Europe over 4 years, aims to assess the diagnostic yield of TESA- (trypomastigote excreted-secreted antigens) blot as a confirmatory technique in patients with inconclusive and discordant results. Of 4939 individuals screened, 1124 (22.7%) obtained positive results and 165 (3.3%) discordant results. Serology was repeated in 88/165 sera and discrepancies were solved in 25/88 (28.4%) cases. Patients without a definitive diagnosis were classified in two different groups: Group 1, including patients with inconclusive results despite retesting (n = 63), and Group 2, including patients with discordant results not retested (n = 77). TESA-blot was performed for all of Group 1 and 39/77 of Group 2 and was positive for 33/63 (52.4%) and 21/39 (53.8%), respectively. Analysis of Group 1 results showed a moderate agreement between results of the ELISA based on native antigen and TESA-blot (κ 0.53). In contrast, a clear disagreement was observed between the ELISA based on recombinant antigens and TESA-blot (κ <0). A sizeable proportion of patients are suspected to have CD with inconclusive results or in whom re-testing is not feasible. TESA-blot was positive in half of these patients, highlighting the need for a confirmatory assay in European centres caring for exposed individuals.
Assuntos
Doença de Chagas/sangue , Doença de Chagas/diagnóstico , Adulto , Idoso , Algoritmos , Biomarcadores , Doença de Chagas/epidemiologia , Doença de Chagas/parasitologia , Doença Crônica , Tomada de Decisão Clínica , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Testes Sorológicos , Espanha/epidemiologia , Adulto JovemRESUMO
Reactivation of Chagas disease in the chronic phase may occur when immunosuppression is established, sometimes resulting in high parasitaemia and severe clinical manifestations such as meningitis and meningoencephalitis. Although this situation is being increasingly described, there is still scarce information. This retrospective observational study was performed in three Tropical Medicine Units of Barcelona (Spain) included in the International Health Programme of the Catalan Health Institute (PROSICS). The objective of the study was to describe epidemiological, clinical, microbiological, prognostic and therapeutic data from patients with Chagas disease and any kind of immunosuppressive condition attended in these three institutions from January 2007 to October 2014. From 1823 patients with Chagas disease attending these three centres during the study period, 38 (2%) had some kind of immunosuppressive condition: 12 patients had human immunodeficiency virus infection, 8 patients had neoplasia, 4 patients underwent organ transplantation and 14 patients had an autoimmune disease. Eight (21.1%) patients had cardiac involvement, and six (15.8%) patients had gastrointestinal involvement. Acute Trypanosoma cruzi infection was detected in two Spanish patients. Thirty-one (81.6%) patients received treatment with benznidazole, of whom 17 (54.8%) had some kind of adverse event. No patient had a severe manifestation or reactivation of Chagas disease. Patients with Chagas disease under immunosuppressive conditions are being increasingly described, especially in non-endemic countries. More information about this topic is required and international consensus in the diagnosis, treatment and follow up of these patients must be established to reduce the morbidity and mortality.
Assuntos
Doença de Chagas/epidemiologia , Hospedeiro Imunocomprometido , Adolescente , Adulto , Idoso , Antiprotozoários/uso terapêutico , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Doença de Chagas/patologia , Criança , Pré-Escolar , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Nitroimidazóis/uso terapêutico , Estudos Retrospectivos , Espanha/epidemiologia , Resultado do Tratamento , Trypanosoma cruzi/isolamento & purificação , Adulto JovemRESUMO
Chagas disease has been increasingly diagnosed in non-endemic countries. This is a prospective observational study performed at the Tropical Medicine Units of the International Health Program of the Catalan Health Institute, Barcelona (PROgrama de Salud Internacional del Instituto Catalán de la Salud, PROSICS Barcelona, Spain), that includes all patients with Chagas disease who attended from June 2007 to May 2012. Clinical and epidemiological data were collected. Overall, 1274 patients were included, the mean age of the patients was 37.7 years, 67.5% were women and 97% came from Bolivia. Thirteen patients had immunosuppressive conditions. The prevalence of cardiac involvement was 16.9%, lower than in previous studies performed in endemic areas (20-60%). Cardiac alterations were found in 33.8% of symptomatic and 14.1% of asymptomatic patients. The prevalence of digestive involvement was 14.8%. The rate of digestive involvement is very different among previous studies because of different diagnostic tools and strategies used. Barium enema alterations were found in 21.4% of symptomatic and 10.3% of asymptomatic patients, and oesophageal alterations were found in 3.7% of symptomatic and in 2.3% of asymptomatic patients. As shown in previous studies, Chagas disease in non-endemic countries affects younger patients and has lower morbidity.
Assuntos
Doença de Chagas/epidemiologia , Doença de Chagas/patologia , Trypanosoma cruzi/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Chagas/parasitologia , Doenças do Sistema Digestório/epidemiologia , Doenças do Sistema Digestório/parasitologia , Doenças do Sistema Digestório/patologia , Emigrantes e Imigrantes , Feminino , Cardiopatias/epidemiologia , Cardiopatias/parasitologia , Cardiopatias/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha/epidemiologia , Adulto JovemRESUMO
No disponible
Assuntos
Humanos , Malária/tratamento farmacológico , Artemisininas/uso terapêutico , Antimaláricos/uso terapêutico , Infusões IntravenosasRESUMO
En los últimos 20 años los medicamentos biotecnológicos han ido teniendo un papel creciente en el tratamiento de muchas enfermedades. Presentan numerosas ventajas respecto a otros medicamentos biológicos, como una enorme disponibilidad, excelente perfil de seguridad respecto a la transmisión de virus y otros patógenos, y la posibilidad de disponer de moléculas modificadas o combinaciones de partes de moléculas distintas con diferente especificidad o afinidad, perfil farmacocinético o menor inmunogenicidad. El ámbito de aplicación de los medicamentos biotecnológicos suele ser hospitalario y el impacto de su introducción está determinado por algunas de sus peculiaridades, entre ellas, su gran disponibilidad y su especificidad. Sin embargo, en algunos casos, las expectativas respecto a su eficacia no se han visto cumplidas e incluso se podría cuestionar si el beneficio obtenido es suficiente para justificar la toxicidad asociada a su uso. El proceso de producción y control de estos medicamentos es costoso y complejo, de ahí que su precio elevado y su utilización terapéutica cada vez más amplia supongan un desafío para los sistemas sanitarios (AU)
In the last 20 years, biotechnological medicinal products have had an increasing role in the treatment of many conditions. These products have several advantages over other biological medicinal products such as potential availability in large quantities, an excellent safety record regarding transmission of viruses or other pathogens and the possibility to have modified molecules or combinations of parts from different molecules to achieve a different specificity or affinity, pharmacokinetic profile or reduced immunogenicity. Biotech medicines are mainly for hospital use and the impact of their introduction is determined by some of their characteristics such as large availability and specificity. However, in some cases, high expectations about their efficacy have not been reached and even their benefit can be questioned considering the toxicity associated with their use. The production process and control of biotech medicines is expensive and complex, therefore, their high price and widespread use is increasingly challenging for healthcare systems (AU)