Desempenho do teste rápido imunocromatográfico (TRI) para o diagnóstico da leishmaniose visceral canina: comparação com outros métodos sorológicos em cães suspeitos de Cuiabá, Mato Grosso, Brasil

O teste rápido imunocromatográfico (TRI) para leishmaniose visceral canina (LVC) foi testado em cães suspeitos da área urbana de Cuiabá. O desempenho do teste foi comparado com RIFI e ELISA e, como padrão ouro, o teste parasitológico direto (TPD). A amostra com 45 cães foi selecionada pelo Centro de Controle de Zoonoses, sendo 23 (51,1%) machos, 34 (75,5%) sem raça definida e com idade estimada inferior a três anos. De acordo com os dados clínicos e os exames laboratoriais, 10 (26,3%) cães foram classificados como expostos, outros 10 (26,3%) como infectados e 18 (47,4%) como doentes. O TRI alcançou os melhores resultados quanto à sensibilidade, 62%, elevada especificidade, 87% e para os valores preditivos positivo e negativo: 83,30% e 81,48%, respectivamente, consolidado pelo coeficiente Kappa igual a 0,50, de concordância moderada. Os resultados confirmaram TRI como um bom preditor de doença e infecção para LVC.The immunochromathographic rapid test (IRT) for canine visceral leishmaniasis (CVL) was tested in suspected dogs from the urban area of Cuiabá. The performance of IRT was compared with IFT and EIE and the direct parasitological test (DPT) as the gold standard. The sample, comprising 45 dogs, was selected by the Zoonosis Control Center. Twenty (51%) were male and thirty-four (75.5%) were both mongrel and had an estimated age of less than three years old. According to clinical data and lab tests: 10 (26.3%) dogs have been classified as exposed or infected and 18 (47.4%) as sick. IRT has achieved the best result for sensibility, 62%, high specificity, 87% and for positive and negative predictive values: 83.3% and negative 81.48%, respectively, reinforced by a k coefficient equal to 0.50, representing substantial agreement

Clinical significance of rare serum autoantibodies in rheumatic diseases: a systematic literature review

The identification of serum autoantibodies is central in the diagnosis of systemic autoimmune rheumatic disease (SARD), and an increasing number of specificities have been detected in the past years. This allows an early diagnosis in the active phases of diseases, with the identification of specific disease subsets that may ultimately improve the disease outcomes. Thanks to the use of old and new laboratory techniques that are becoming increasingly available worldwide, the number of rheumatic patients with a specific autoantibody is increasing and this is improving also our knowledge of disease trigger mechanisms. The paradigmatic example is the plethora of serum autoantibodies described in polymyositis and dermatomyositis, coined myositis-specific antibodies (MSA) which include antibodies directed against tRNA synthetases, anti-SRP, anti-Mi-2, and anti-TIF-1γ and can discriminate disease subtypes, particularly when associated with the risk of cancer. As a further example, anti-HMGCR antibodies have been reported in several studies in association with necrotizing autoimmune myositis that may follow statin use. To clarify the current knowledge on these rare specificities, we performed a systematic literature review. We focused on the main features associated to specific autoantibodies that are rarely identified in rheumatic disease, to increase the awareness and scientific knowledge on these autoantibodies in different ethnic groups worldwide.Fil: Ceribelli, Angela. Humanitas Research Hospital; Italia. Università degli Studi di Milano; ItaliaFil: Isailovic, Natasa. Humanitas Research Hospital; ItaliaFil: De Santis, Maria. Humanitas Research Hospital; ItaliaFil: Generali, Elena. Humanitas Research Hospital; ItaliaFil: Gorlino, Carolina Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Humanitas Research Hospital; ItaliaFil: Palermo, Bianca. Humanitas Research Hospital; ItaliaFil: Selmi, Carlo. Università degli Studi di Milano; Italia. Humanitas Research Hospital; Itali

Hepatitis E Virus Occurrence in Pigs Slaughtered in Italy

In Europe, foodborne transmission has been clearly associated to sporadic cases and small clusters of hepatitis E in humans linked to the consumption of contaminated pig liver sausages, raw venison, or undercooked wild boar meat. In Europe, zoonotic HEV-genotype 3 strains are widespread in pig farms but little information is available on the prevalence of HEV positive pigs at slaughterhouse. In the present study, the prevalence of HEV-RNA positive pigs was assessed on 585 animals from 4 abattoirs located across Italy. Twenty-one pigs (3.6%) tested positive for HEV in either feces or liver by real-time RT-PCR. In these 21 pigs, eight diaphragm muscles resulted positive for HEV-RNA. Among animals collected in one abattoir, 4 out of 91 plasma tested positive for HEV-RNA. ELISA tests for the detection of total antibodies against HEV showed a high seroprevalence (76.8%), confirming the frequent exposure of pigs to the virus. The phylogenetic analyses conducted on sequences of both ORF1 and ORF2 fragments, shows the circulation of HEV-3c and of a novel unclassified subtype. This study provides information on HEV occurrence in pigs at the slaughterhouse, confirming that muscles are rarely contaminated by HEV-RNA compared to liver, which is the most frequently positive for HEV

DECLINE OF PREVALENCE OF RESISTANCE ASSOCIATED SUBSTITUTIONS TO NS3 AND NS5A INHIBITORS AT DAA- FAILURE IN HEPATITIS C VIRUS IN ITALY OVER THE YEARS 2015 TO 2018

Background: A minority of patients fails to eliminate HCV and resistance-associated substitutions (RASs) are commonly detected at failure of interferon-free DAA regimens . Methods: Within the Italian network VIRONET-C, the prevalence of NS3/NS5A/NS5B RASs was retrospectively evaluated in patients who failed an EASL recommended DAA-regimen in 2015-2018 . The geno2pheno system and Sorbo MC et al. Drug Resistance Updates 2018 were used to infer HCV- genotype/subtype and predict drug resistance . The changes in prevalence of RASs over time were evaluated by chi-square test for trend, predictors of RASs at failure were analysed by logistic regression . Results: We included 386 HCV infected patients: 75% males, median age was 56 years (IQR 52-61), metavir fibrosis stage F4 in 76%; 106 (28%) were treatment- experienced: 91 (86%) with IFN-based treatments, 26 (25%) with DAAs. Patients with HIV and HBV coinfection were 10% (33/317) and 8% (6/72), respectively. HCV genotype was 1b in 122 pts (32%), 3 in 109 (28%), 1a in 97 (25%), 4 in 37 (10%), 2 in 21 (5%). DAA regimens were: LDV/SOF in 115 (30%), DCV/SOF in 103 (27%), 3D in 83 (21%), EBR/GRZ in 32 (8%), VEL/SOF in 29 (7%), GLE/PIB in 18 (5%) and 2D in 6 (2%); ribavirin was administered in 123 (32%) . The NS5A fasta-sequence was available for all patients, NS5B for 361 (94%), NS3 for 365 (95%) . According to the DAA failed the prevalence of any RASs was 90%, namely 80/135 (59%) in NS3, 313/359 (87%) in NS5A, 114/286 (40%) in NS5B . The prevalence of any RASs significantly declined from 2015 to 2018 (93% vs 70%, p=0.004): NS5A RASs from 90% to 72% (p=0 .29), NS3 RASs from 74% to 18% (p<0 .001), while NS5B RASs remained stable . Independent predictors of any RASs included advanced fibrosis (AOR 6.1, CI 95% 1.8-20.3, p=0 .004) and genotype (G2 vs G1a AOR 0 .03, CI 95% 0 .002- 0 .31, p=0 .004; G3 vs G1a AOR 0 .08, CI 95% 0 .01-0 .62, p=0 .02; G4 vs G1a AOR 0 .05, CI 95% 0 .006-0 .46, p=0 .008), after adjusting for age, previous HCV treatment and year of genotype . Notably, full activity was predicted for GLE/PIB in 75% of cases and for at least two components of VEL/SOF/VOX in 53% of cases, no case with full-resistance to either regimen was found . Conclusion: Despite decreasing prevalence over the years, RASs remain common at virological failure of DAA treatment, particularly in patients with the highest grade of liver fibrosis. The identification of RASs after failure could play a crucial role in optimizing retreatment strategies

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Dengue no estado do rio de janeiro, 1986-2012: busca por um marcador precoce de gravidade

Made available in DSpace on 2018-05-08T15:53:25Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) bianca_goncalves_ioc_dout_2017.pdf: 5996950 bytes, checksum: bc8ca5293834aedf257ec2407760924a (MD5)Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Desde a reintrodução do vírus dengue (DENV) no Brasil em 1981, mais de 12.500.000 casos da doença já foram reportados, representando um grave problema de saúde pública para o país. A infecção por DENV pode ser assintomática ou sintomática, variando de uma forma branda a formas graves, como a febre hemorrágica da dengue e a síndrome do choque da dengue. Em 2009, a OMS estabeleceu um novo critério de classificação de casos que tem por objetivo aprimorar a triagem e o tratamento adequado aos pacientes. De acordo com esses critérios, os pacientes são classificados em dengue com sinais de alerta, dengue sem sinais de alerta e dengue grave. A detecção precoce de dengue grave em pacientes sem sinais de alerta que podem evoluir para a forma hemorrágica grave é muito importante para a escolha de uma terapia de suporte intensivo apropriada, uma vez que vacinas ou terapias específicas com eficácia comprovada não estão disponíveis. Buscando identificar um marcador de gravidade durante a fase aguda (0-5 dias de doença), correlacionamos as variáveis sexo, faixa etária, número de dias de doença, resposta imune, viremia, antigenemia da NS1, sorotipo e linhagem de DENV-2 à apresentação clínica da dengue, nos grupos \201Cdengue sem sinais de alerta\201D (DSSA) e \201Cdengue com sinais de alerta/dengue grave\201D(DCSA/DG) de pacientes residentes no estado do Rio de Janeiro. Resposta imune foi classificada por ELISA in-house, antigenemia determinada por quantificação da NS1 e viremia quantificada por PCR em tempo real. Do total de pacientes, com DSSA e DCSA/DG, 32,9% (108/328) apresentaram sinais de alerta/dengue grave (DCSA/DG), sendo que 58,3% (63/108) destes pacientes respondiam a uma primo-infecção Do total de pacientes, com DSSA e DCSA/DG, 61,9% (200/323) foram classificados com infecção primária (perda de 5 amostras de soro). No estudo 1, os sinais de alerta/dengue grave foram mais frequentes em pacientes com 4-5 dias de doença (p=0,033). Pacientes de 13-19 anos tiveram chance 75% maior de apresentar DCSA/DG (p60 years of age (p=0.001) and with 0-1 day of disease (p=0.013). DENV-4 had higher levels of viremia (p <0.0001) and higher viral load in infections with 0-1 day of disease (p<0.0001). In study 3, DENV-2 (lineage I) presented major viremia in primary infections (p=0.015). Patients infected with DENV-2 lineage II and aged \226412 years were more likely to develop warning signs/severe dengue (p=0.028), and higher viremia with 0-1 day of infection (p=0.002). Given the epidemiological characteristics of the hyperendemic Rio de Janeiro state, and considering that a large number of DENV-3 susceptible individuals have accumulated over several years, surveillance plays a very important role in detecting early the re-emergence of this serotype, as already demonstrated in the reemergence of DENV-1 and DENV-2

Canine Visceral Leishmaniasis in Cuiabá Urban Area MT: Comparing Laboratory Techniques, Attempt to Develop Methodology for Diagnosis and Characterization of the Species of Leishmania Stock in the Sample Selected

Made available in DSpace on 2011-05-04T12:36:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2010Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Rio de Janeiro, RJ, Brasil.Segundo o Ministério da Saúde, o diagnóstico laboratorial da Leishmaniose Visceral Canina (LVC) permanece como um problema para os serviços de saúde, e está relacionado a três fatores: variedade de sinais clínicos semelhantes aos observados em outras doenças infecciosas, alterações histopatológicas inespecíficas e a inexistência de um teste de diagnóstico próximo a 100% de especificidade e sensibilidade. Esta questão, associada ao fato de haver registro de cães infectados por Leishmania sp, agente etiológico da LVC, desde o final da década de 1990 em Mato Grosso, motivou a realização deste trabalho. O objetivo geral desta dissertação foi analisar amostras de cães com suspeita clínica ou não de leishmaniose visceral, recolhidos pelo Centro de Controle de Zoonoses (CCZ), oriundos de área urbana de Cuiabá (MT), a partir da comparação de técnicas laboratoriais de RIFI, ELISA, teste rápido imunocromatográfico DPPTM e cultivo in vitro com o exame parasitológico direto (esfregaço de medula óssea), desenvolver uma metodologia de diagnóstico utilizando, como substrato, o papel de filtro FTA® Card embebido com o aspirado de tecido subcutâneo dos animais e caracterizar a espécie de Leishmania circulante. Foram analisados 45 cães, de ambos os sexos e de diferentes raças. (...) A combinação do aspirado de tecido subcutâneo dos cães, em papel de filtro FTA® Card, com a PCR não obteve resultados positivos nesta pesquisa. Portanto, esta metodologia deve ser aprimorada mediante novos testes. A priori, com abordagem diferente para a coleta do aspirado de tecido subcutâneo em cães e realização da PCR. A espécie de Leishmania, caracterizada pela enzima 6PGDH, circulante em cinco cães amostrados, provenientes de área urbana de Cuiabá, foi a Leishmania (Leishmania) infantum.According to the Ministry of Health, the laboratory diagnosis of Canine Visceral Leishmaniasis (CVL) remains as a problem for health services, and is linked to three factors: variety of clinical evidence similar to those observed in other infectious diseases, histopathologic-unspecific changes and the lack of a diagnostic test near 100% specificity and sensitivity. This issue associated with having infected dogs record for Leishmania sp, etiological microorganism of the CVL, since the late 1990s in Mato Grosso state, motivated this study. The main purpose of this dissertation was analyzing samples of dogs with clinical suspicion or not with leishmaniasis, collected by Zoonoses Control Center (ZCC) from Cuiabá (MT) urban area by comparing laboratory techniques IFR, ELISA, rapid test imunocromatographic DPPTM and cultivation in vitro with parasitological direct examination (smear of bone marrow), to develop a methodology for diagnosis using as substrate, the filter paper FTA ® card wet and embedded with the infiltrate of subcutaneous tissue of animals and characterize the species of Leishmania stock present in the culture. The results showed that 45 dogs were examined, of both sexes and of different races. The clinical evidences recorded in dogs sampled from Cuiabá urban area were, in descending order of frequency: desquamation (53.33%), alopecia (44.44%), injuries (40%), cachexia (26.67%), onychogryphosis (26.67%), mucosal pale (26.67%), keratoconjunctivitis, (26.67%) and apathy (13.33%). The positive results obtained by direct parasitological techniques (gold standard), cultivation in vitro IFR, ELISA and DPPTM accounted for 37.21% (16/43), 44.44% (8/18), 84.44% (38/45), 42.22% (19/45) and 46.67% (21/45), respectively. The rapid test sensitivity = imunocromatographic DPPTM (68.42%, specificity = 87.5%, accurate = 73.07%, k = 0.57) proved to be more sensitive, more specific and with greater reliability than IFR (sensitivity = 44.44%, specificity = 100%, accurate = 53.49%, k = 0.21) and ELISA (sensitivity = 58.52%, specificity = 76.92%, accurate = 69.77%, k = 0.36). The combination of subcutaneous infiltrate dogs tissues in filter paper FTA ® card with the PCR did not succeed in this poll. Therefore, this methodology must be enhanced by further testing. A priori with different approach to the collection of induction of subcutaneous in dogs tissues and the proceedings of PCR. The species of Leishmania, characterized by the enzyme 6PGDH, stock in five dogs sampled from Cuiabá, urban area was Leishmania (Leishmania) infantum