Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: The ZIKAlliance consortium

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmissio

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Dementia in Latin America : paving the way towards a regional action plan

Regional challenges faced by Latin American and Caribbean countries (LACs) to fight dementia, such as heterogeneity, diversity, political instabilities, and socioeconomic disparities, can be addressed more effectively grounded in a collaborative setting based on the open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking and translational research) and align them to current global strategies to translate regional knowledge into actions with transformative power. Then, by characterizing genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions and mapping these to the above challenges, we provide the basic mosaics of knowledge that will pave the way towards a KtAF. We describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Inquérito epidemiológico sobre conceitos de zoonoses parasitárias para professores de escolas municipais do ensino infantil de Araçatuba-SP

Considerando a relevância da instrução e do grau de informação das professoras em escolas municipais de ensino infantil (EMEI’S), a elevada ocorrência de endoparasitoses em humanos e a situação endêmica da leishmaniose visceral canina na região de Araçatuba, foi elaborado este estudo objetivando investigar o grau de conhecimento daquelas sobre zoonoses parasitárias. Foram visitadas trinta EMEI’S de Araçatuba, onde foi aplicado a 85 professoras um questionário sobre parasitoses. A análise estatística descritiva revelou que 96,47% (82 em 85) das professoras responderam que andar descalço pode interferir na infecção helmíntica e 85,88% (73/85) responderam que roer unhas pode interferir. Verificou-se que 44,71% (38/85) delas ignoravam a patogenia de helmintoses e 63,53% (54/85) não administravam anti-helmintícos em pequenos animais. A participação dos felinos na transmissão da toxoplasmose era de conhecimento de 92,94% (79/85), das quais 82,35% (70/85) desconheciam as vias de transmissão. O cão foi incriminado como disseminador desta enfermidade por 80,00% (68/85) das entrevistadas, e apenas 4,71% (4/85) citaram a ingestão de produtos cárneos como outra via de transmissão do Toxoplasma gondii, sendo que 67,06% (57/85) desconheciam o assunto. Quanto ao calazar, 91,76% (78/85) afirmaram que cães são transmissores, mas 58,82% (50/85) não sabiam como, e 60,00% (51/85) preconizaram como medida preventiva exclusiva a limpeza ambiental. A partir dos dados obtidos, podemos inferir que existe a necessidade da implantação de um programa de educação comunitária direcionado ao aprimoramento dos conceitos básicos sobre controle e prevenção de zoonoses parasitárias

Inquérito epidemiológico sobre conceitos de zoonoses parasitárias para professores de escolas municipais do ensino infantil de Araçatuba-SP

Considering the relevance of the educational degree and the amount of information held by the teachers in municipal primary schools (EMEI’S), the elevated occurrences of endoparasitosis in humans, and the endemic situation of canine visceral leishmaniosis in Araçatuba region, this study was elaborated with the aim of investigating their degree of knowledge regarding parasitological zoonosis (infestations). Thirty EMEI’S in Araçatuba were visited, in which 85 teachers were selected randomly and they were given a questionnaire that would test their knowledge about parasitosis. The descriptive statistic analysis revealed that 96.47% (82 out of 85) of the teachers said that walking barefoot can interfere in helminthic infection. 85.88% (73/85) said that biting fingernails can facilitate helminthic infection. 44.71% (38/85) knew nothing about helminthic pathogenesis. 63.53% (54/85) didn’t give helminthic pills to their pets (small animals). 92.74% (79/85) knew about the role played by cats in the transmission of toxoplasmosis. 82.35% (70/85) did not know the actual route of transmission in toxoplasmosis. 80.00% (68/85) blamed the dog as the spreader of this disease and only 4.71% (4/85) stated that meat and its byproducts as a possible source of transmission of Toxoplasma gondii. 67.06% (57/85) did not know anything about it. Concerning kalazar 91.76% (78/85) said dogs are transmitters of kalazar but 58.82%, (50/85) said they did not know how it was transmitted and 60.00% (51/85) said exclusive environmental cleaning would prevent the disease. Based on the results evidenced, we can conclude that there is a need of implanting a community educational campaign, towards the improvement of basic concepts on control and prevention of parasitic zoonosis.Considerando la importancia de la instrucción y del grado de información de las educadoras de las escuelas municipales de educación infantil (EMEI´S), la frecuencia alta de endoparasitoses en humanos y la situación endémica de leishmaniose visceral canina en la región de Araçatuba, fue realizado este estudio con el objetivo de investigar el grado de conocimiento de las profesoras sobre “zoonoses” parasitarias. Fueron visitadas treinta EMEI´S de Araçatuba, donde fueron aplicados cuestionarios sobre parasitoses a 85 profesoras. El análisis estadístico descrito reveló que 96.47% (82/85) y 85.88%(73/85) de las profesoras respondieron que caminar descalzo y comer las uñas pueden interferir en la infección ‘helmíntica” , respectivamente. Se verificó que 38 (44.71%) desconocían la patogenia de “helmintotes” y 54 (63.53%) de las profesoras no administran “anti-helmintícos” en animales pequeños. La participación de los felinos en la transmisión de la toxoplasmose era de conocimiento de 92.94% (79/85) de las profesoras, de las cuales 82.35% (70/85) desconocían las vias de transmisión. El canino fue indicado como diseminador de esta enfermedad por 68 (80%) de las entrevistadas y apenas cuatro (4.71%) indicaron el consumo de productos de carnes como otra canal de transmisión del Toxoplasma gondii, siendo que 57 (67.06%) desconocían el asunto. En relación al calazar, 78 (91,76%) de las personas afirmaron que los canes son transmisores, pero 50 (58.82%) no sabían como, y 51 (60%) indicaron como medida de prevención exclusiva la limpieza del ambiente. A partir de los dados obtenidos podemos deducir que existe la necesidad de implementar un programa de educación comunitária orientado al aprendizaje de conceptos básicos sobre control y prevención de “zoonoses” parasitarias.Considerando a relevância da instrução e do grau de informação das professoras em escolas municipais de ensino infantil (EMEI’S), a elevada ocorrência de endoparasitoses em humanos e a situação endêmica da leishmaniose visceral canina na região de Araçatuba, foi elaborado este estudo objetivando investigar o grau de conhecimento daquelas sobre zoonoses parasitárias. Foram visitadas trinta EMEI’S de Araçatuba, onde foi aplicado a 85 professoras um questionário sobre parasitoses. A análise estatística descritiva revelou que 96,47% (82 em 85) das professoras responderam que andar descalço pode interferir na infecção helmíntica e 85,88% (73/85) responderam que roer unhas pode interferir. Verificou-se que 44,71% (38/85) delas ignoravam a patogenia de helmintoses e 63,53% (54/85) não administravam anti-helmintícos em pequenos animais. A participação dos felinos na transmissão da toxoplasmose era de conhecimento de 92,94% (79/85), das quais 82,35% (70/85) desconheciam as vias de transmissão. O cão foi incriminado como disseminador desta enfermidade por 80,00% (68/85) das entrevistadas, e apenas 4,71% (4/85) citaram a ingestão de produtos cárneos como outra via de transmissão do Toxoplasma gondii, sendo que 67,06% (57/85) desconheciam o assunto. Quanto ao calazar, 91,76% (78/85) afirmaram que cães são transmissores, mas 58,82% (50/85) não sabiam como, e 60,00% (51/85) preconizaram como medida preventiva exclusiva a limpeza ambiental. A partir dos dados obtidos, podemos inferir que existe a necessidade da implantação de um programa de educação comunitária direcionado ao aprimoramento dos conceitos básicos sobre controle e prevenção de zoonoses parasitárias

Ocorrência de Leishmania spp. em felinos do município de Araçatuba, SP Occurrence de Leishmania spp. in domestic cats from Araçatuba, SP

Este trabalho teve como objetivo comparar a ocorrência de Leishmania spp. em gatos por dois métodos (citológico e sorológico), bem como associar a ocorrência deste protozoário com as variáveis sexo, idade e raça. Amostras séricas de 283 felinos domésticos foram testadas pela Reação de Imunofluorescência Indireta (RIFI), e o exame parasitológico direto de linfonodos também foi realizado para a verificação da positividade para Leishmania spp. Ocorrência de 0,7% (2/283) foi observada nos felinos examinados, por meio de imprint de linfonodos e nenhum animal apresentou títulos de anticorpos para Leishmania spp. As duas fêmeas positivas eram sem raça definida, sendo uma jovem e outra adulta. Por meio dos resultados obtidos, não foi constatada diferença estatisticamente significante em relação às variáveis sexo, raça e idade nos gatos desta pesquisa (p > 0,05). Ocorrência de Leishmania spp. nos gatos deste estudo foi baixa. Devido a esta baixa incidência sugere-se que estes não assumem importância epidemiológica na área do estudo.<br>This study had the purpose to compare the occurrence of Leishmania spp. in felines through two methods (cytological and serological), as well as to associate the occurrence of this protozoan with the sex, age and breed variables. Serum samples from 283 domestic felines were processed by means of Indirect Immunofluorescence Reaction (IIR), and the direct parasitological test for linfonodes was also carried out in order to verify positivity for Leishmania spp. Occurrence of 0.7% (2/283) was observed in the tested felines by means of linfonode imprinting and no animal showed title of antibodies for Leishmania spp. The two positive females were mongrel, a young female and an adult female feline. From the obtained results, no statistically significant difference was observed as regards the sex, breed and age variables in this research (p > 0.05). Occurrence of Leishmania spp. in the cats of this study was low. Such low incidence suggests that these hosts has no epidemiological relevance in the study area

Ocorrência de Leishmania spp. em felinos do município de Araçatuba, SP

Este trabalho teve como objetivo comparar a ocorrência de Leishmania spp. em gatos por dois métodos (citológico e sorológico), bem como associar a ocorrência deste protozoário com as variáveis sexo, idade e raça. Amostras séricas de 283 felinos domésticos foram testadas pela Reação de Imunofluorescência Indireta (RIFI), e o exame parasitológico direto de linfonodos também foi realizado para a verificação da positividade para Leishmania spp. Ocorrência de 0,7% (2/283) foi observada nos felinos examinados, por meio de imprint de linfonodos e nenhum animal apresentou títulos de anticorpos para Leishmania spp. As duas fêmeas positivas eram sem raça definida, sendo uma jovem e outra adulta. Por meio dos resultados obtidos, não foi constatada diferença estatisticamente significante em relação às variáveis sexo, raça e idade nos gatos desta pesquisa (p > 0,05). Ocorrência de Leishmania spp. nos gatos deste estudo foi baixa. Devido a esta baixa incidência sugere-se que estes não assumem importância epidemiológica na área do estudo.This study had the purpose to compare the occurrence of Leishmania spp. in felines through two methods (cytological and serological), as well as to associate the occurrence of this protozoan with the sex, age and breed variables. Serum samples from 283 domestic felines were processed by means of Indirect Immunofluorescence Reaction (IIR), and the direct parasitological test for linfonodes was also carried out in order to verify positivity for Leishmania spp. Occurrence of 0.7% (2/283) was observed in the tested felines by means of linfonode imprinting and no animal showed title of antibodies for Leishmania spp. The two positive females were mongrel, a young female and an adult female feline. From the obtained results, no statistically significant difference was observed as regards the sex, breed and age variables in this research (p > 0.05). Occurrence of Leishmania spp. in the cats of this study was low. Such low incidence suggests that these hosts has no epidemiological relevance in the study area