Estudo de um antígeno intradérmico para o diagnóstico da cisticercose: nota prévia

An intradermic antigen for the diagnosis of cysticercosis is being proposed. The manner of preparation and application is also shown. The reading of the result is proceeded 30 minutes after the intradermic injection by measuring the papule's diameter. Up to now the antigen has been tested on 31 cerebral cysticercotic patients and on 64 non-infested persons: The papule mean diameter was 14,6 mm (s.d. ± 7,3 mm) for the patients and 4,9 mm (s.d. ± 1,8 mm) for the control group. There were no negative reactions among the patients and 26,5% of the non-infested presented no reaction whatsoever to the antigen. Later complications were not refered. Testing on patients with cestoid enteric infestation is now being carried out. It seems that the antigen has fairly good sensibility and fulfils the necessary epidemiological requirements of easy preparation, simples application and reading, inocuity, sensitiveness and low cost.Propõe-se um antígeno intradérmico para o diagnóstico da cisticercose, mostrando a maneira de aplicá-lo e prepará-lo. A leitura é feita após 30 minutos de aplicada a injeção, medindo-se o diâmetro da pápula. O antígeno já foi testado em 31 pacientes de cisticercose cerebral e em 64 pessoas não parasitadas; os cisticercóticos apresentaram pápulas medindo em média 14,6 mm, com um desvio padrão de 7,3 mm, enquanto que nos "normais" a pápula mediu 4,9 ± 1,8 mm. Entre os cisticercóticos não houve reações negativas e entre os "normais" 26,5% não reagiram ao antígeno. Não foram narradas complicações posteriores. Encontram-se em fase inicial os testes em portadores de cestóides intestinais. O antígeno parece ter boa sensibilidade e possuir os requisitos necessários para ter valor epidemiológico: economia, fácil obtenção, aplicação e leitura simples, inocuidade, sensibilidade

An intradermal antigen for cysticercosis diagnosis

A new antigen for a cutaneous test used for cyticercosis diagnosis is described. The author refers to technical details of antigen preparation and the results obtained in tests performed on 64 controls, on 18 subjects infected with Taenia, on 34 subjects with cerebral cysticercosis and on 51 subjects with Hymenolepis nana. The antigen is considered specific, sensible, innocuous and very easy to apply. The test is pointed out as being the test of choice in epidemiologic studies.É descrito novo antígeno para teste cutâneo no diagnóstico da cisticercose. São relatados os resultados obtidos em experimentação realizada em 64 pessoas não parasitadas, em 18 portadores de ténia, em 34 de cisticercose cerebral e em 51 de Hymenolepis nana. Após considerações sobre a especificidade, sensibilidade, facilidade de aplicação e leitura e inocuidade do antígeno proposto, é indicado como teste de triagem em estudos epidemiológicos

Aumento do poder discriminatório de indicadores de saúde (coeficientes de mortalidade geral e mortalidade infantil)

A study was made to demonstrate the increase of the discriminative power of two sanitary rates which are most easily calculated in all areas of the world: the general mortality rate and the infantile mortality rate. The manner to obtain this increase of discriminatory power consists in calculating the difference between the infantile mortality rate and the general mortality rate. Statistically analysed and taking into consideration data from developed countries and those undergoing development during the same period, as well as throughout different periods, this difference was more discriminatory than any of the two separately and when used together with one or both, the power of discrimination is increased significantly.Foi feito estudo demonstrando o aumento do poder discriminatório dos dois coeficientes sanitários mais facilmente calculados em todas as áreas do mundo: o coeficiente de mortalidade geral e o coeficiente da mortalidade infantil. A maneira de se obter esse aumento do poder discriminatório consiste em se calcular a diferença entre estes dois coeficientes de mortalidade. Analisada estatisticamente, usando dados de países desenvolvidos e em desenvolvimento na mesma época e em épocas diversas, essa diferença demonstrou ser mais discriminatória que qualquer um dos dois isoladamente e quando usada juntamente com um dos dois ou com ambos aumenta significativamente o poder de discriminação

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Publisher Copyright: © 2021 The Authors, some rights reserved.Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.Peer reviewe

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

SignificanceThere is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged 4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute; The Rockefeller University; the St. Giles Foundation; the NIH (Grants R01AI088364 and R01AI163029); the National Center for Advancing Translational Sciences; NIH Clinical and Translational Science Awards program (Grant UL1 TR001866); a Fast Grant from Emergent Ventures; Mercatus Center at George Mason University; the Yale Center for Mendelian Genomics and the Genome Sequencing Program Coordinating Center funded by the National Human Genome Research Institute (Grants UM1HG006504 and U24HG008956); the Yale High Performance Computing Center (Grant S10OD018521); the Fisher Center for Alzheimer’s Research Foundation; the Meyer Foundation; the JPB Foundation; the French National Research Agency (ANR) under the “Investments for the Future” program (Grant ANR-10-IAHU-01); the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (Grant ANR-10-LABX-62-IBEID); the French Foundation for Medical Research (FRM) (Grant EQU201903007798); the French Agency for Research on AIDS and Viral hepatitis (ANRS) Nord-Sud (Grant ANRS-COV05); the ANR GENVIR (Grant ANR-20-CE93-003), AABIFNCOV (Grant ANR-20-CO11-0001), CNSVIRGEN (Grant ANR-19-CE15-0009-01), and GenMIS-C (Grant ANR-21-COVR-0039) projects; the Square Foundation; Grandir–Fonds de solidarité pour l’Enfance; the Fondation du Souffle; the SCOR Corporate Foundation for Science; The French Ministry of Higher Education, Research, and Innovation (Grant MESRI-COVID-19); Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM; and the University Paris Cité. P. Bastard was supported by the FRM (Award EA20170638020). P. Bastard., J.R., and T.L.V. were supported by the MD-PhD program of the Imagine Institute (with the support of Fondation Bettencourt Schueller). Work at the Neurometabolic Disease lab received funding from Centre for Biomedical Research on Rare Diseases (CIBERER) (Grant ACCI20-767) and the European Union's Horizon 2020 research and innovation program under grant agreement 824110 (EASI Genomics). Work in the Laboratory of Virology and Infectious Disease was supported by the NIH (Grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1), a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Infanta Leonor University Hospital supported the research of the Department of Internal Medicine and Allergology. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (Grant PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (Grant RECOVER WP 6). This work was also partly supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research, NIH (Grants ZIA AI001270 to L.D.N. and 1ZIAAI001265 to H.C.S.). This program is supported by the Agence Nationale de la Recherche (Grant ANR-10-LABX-69-01). K.K.’s group was supported by the Estonian Research Council, through Grants PRG117 and PRG377. R.H. was supported by an Al Jalila Foundation Seed Grant (Grant AJF202019), Dubai, United Arab Emirates, and a COVID-19 research grant (Grant CoV19-0307) from the University of Sharjah, United Arab Emirates. S.G.T. is supported by Investigator and Program Grants awarded by the National Health and Medical Research Council of Australia and a University of New South Wales COVID Rapid Response Initiative Grant. L.I. reports funding from Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e co-morbidità”). This research was partially supported by the Instituto de Salud Carlos III (Grant COV20/0968). J.R.H. reports funding from Biomedical Advanced Research and Development Authority (Grant HHSO10201600031C). S.O. reports funding from Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development (Grant JP20fk0108531). G.G. was supported by the ANR Flash COVID-19 program and SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University iCOVID programs. The 3C Study was conducted under a partnership agreement between INSERM, Victor Segalen Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also supported by the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, Direction générale de la Santé, Mutuelle Générale de l’Education Nationale, Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Program “Cohortes et collections de données biologiques.” S. Debette was supported by the University of Bordeaux Initiative of Excellence. P.K.G. reports funding from the National Cancer Institute, NIH, under Contract 75N91019D00024, Task Order 75N91021F00001. J.W. is supported by a Research Foundation - Flanders (FWO) Fundamental Clinical Mandate (Grant 1833317N). Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. Work at Vall d’Hebron was also partly supported by research funding from Instituto de Salud Carlos III Grant PI17/00660 cofinanced by the European Regional Development Fund (ERDF/FEDER). C.R.-G. and colleagues from the Canarian Health System Sequencing Hub were supported by the Instituto de Salud Carlos III (Grants COV20_01333 and COV20_01334), the Spanish Ministry for Science and Innovation (RTC-2017-6471-1; AEI/FEDER, European Union), Fundación DISA (Grants OA18/017 and OA20/024), and Cabildo Insular de Tenerife (Grants CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). T.H.M. was supported by grants from the Novo Nordisk Foundation (Grants NNF20OC0064890 and NNF21OC0067157). C.M.B. is supported by a Michael Smith Foundation for Health Research Health Professional-Investigator Award. P.Q.H. and L. Hammarström were funded by the European Union’s Horizon 2020 research and innovation program (Antibody Therapy Against Coronavirus consortium, Grant 101003650). Work at Y.-L.L.’s laboratory in the University of Hong Kong (HKU) was supported by the Society for the Relief of Disabled Children. MBBS/PhD study of D.L. in HKU was supported by the Croucher Foundation. J.L.F. was supported in part by the Evaluation-Orientation de la Coopération Scientifique (ECOS) Nord - Coopération Scientifique France-Colombie (ECOS-Nord/Columbian Administrative department of Science, Technology and Innovation [COLCIENCIAS]/Colombian Ministry of National Education [MEN]/Colombian Institute of Educational Credit and Technical Studies Abroad [ICETEX, Grant 806-2018] and Colciencias Contract 713-2016 [Code 111574455633]). A. Klocperk was, in part, supported by Grants NU20-05-00282 and NV18-05-00162 issued by the Czech Health Research Council and Ministry of Health, Czech Republic. L.P. was funded by Program Project COVID-19 OSR-UniSR and Ministero della Salute (Grant COVID-2020-12371617). I.M. is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies (PID); by the Katholieke Universiteit Leuven C1 Grant C16/18/007; by a Flanders Institute for Biotechnology-Grand Challenges - PID grant; by the FWO Grants G0C8517N, G0B5120N, and G0E8420N; and by the Jeffrey Modell Foundation. I.M. has received funding under the European Union’s Horizon 2020 research and innovation program (Grant Agreement 948959). E.A. received funding from the Hellenic Foundation for Research and Innovation (Grant INTERFLU 1574). M. Vidigal received funding from the São Paulo Research Foundation (Grant 2020/09702-1) and JBS SA (Grant 69004). The NH-COVAIR study group consortium was supported by a grant from the Meath Foundation.Peer reviewe

Índices para estimar o tempo transcorrido entre o surto hemorrágico subaracnóideo e a colheita de líquido cefalorraqueano

O autor simulou, experimentalmente, acidente vascular cerebral hemorrágico em cães injetando sangue do próprio animal no espaço subaracnóideo, colhendo amostras diárias de LCR durante 14 dias, sendo estudada a evolução das concentrações de oxiemoglobina e de bilirrubina, empregando métodos espectrofotométricos. Define um coeficiente hemoglobínico como a relação entre a concentração de oxiemoglobina e o total de pigmentos do LCR e um índice hemoglobina-bilirrubina como a relação entre as concentrações de oxiemoglobina e bilirrubina. Depois do tratamento estatístico, chega à conclusão de que ambos permitem estimar o tempo transcorrido desde o surto hemorrágico subaracnóideo e a colheita de LCR. São apresentadas sugestões quanto à aplicabilidade prática destes indicadores em Neurologia e Medicina Preventiva

Antígeno intradérmico para diagnóstico de cisticercose

É descrito novo antígeno para teste cutâneo no diagnóstico da cisticercose. São relatados os resultados obtidos em experimentação realizada em 64 pessoas não parasitadas, em 18 portadores de ténia, em 34 de cisticercose cerebral e em 51 de Hymenolepis nana. Após considerações sobre a especificidade, sensibilidade, facilidade de aplicação e leitura e inocuidade do antígeno proposto, é indicado como teste de triagem em estudos epidemiológicos

Índices para estimar o tempo transcorrido entre o surto hemorrágico subaracnóideo e a colheita de líquido cefalorraqueano Appraisement of the time elapsed between cerebro-vascular accidents and cerebrospinal fluid examination. An experimental study

O autor simulou, experimentalmente, acidente vascular cerebral hemorrágico em cães injetando sangue do próprio animal no espaço subaracnóideo, colhendo amostras diárias de LCR durante 14 dias, sendo estudada a evolução das concentrações de oxiemoglobina e de bilirrubina, empregando métodos espectrofotométricos. Define um coeficiente hemoglobínico como a relação entre a concentração de oxiemoglobina e o total de pigmentos do LCR e um índice hemoglobina-bilirrubina como a relação entre as concentrações de oxiemoglobina e bilirrubina. Depois do tratamento estatístico, chega à conclusão de que ambos permitem estimar o tempo transcorrido desde o surto hemorrágico subaracnóideo e a colheita de LCR. São apresentadas sugestões quanto à aplicabilidade prática destes indicadores em Neurologia e Medicina Preventiva.<br>Hemorrhagic cerebro-vascular accidents were simulated in dogs by injecting their own blood in the subarachnoidal space. Gathering daily samples of cerebrospinal fluid during 14 days the evolution of the concentrations of oxyhemoglobin and bilirubin using the spectrosphotometric method was studied. The author defines hemoglobin coefficient as being the relatinship between the oxyhemoglobin concentration and the sum of the cerebrospinal fluid pigments and the hemoglobin-bilirubin index as the relationship between the oxyhemoglobin and the bilirubin concentration. After statistical treatment the author concludes that both permit to calculate the time span between the subarachnoidal hemorrhage and the examination of the cerebrospinal fluid. Some suggestions on the practical applicability of these indexes in Clinical Neurology and Preventive Medicine are discussed