Efficacy and safety of Butantan-DV in participants aged 2-59 years through an extended follow-up: results from a double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil.

BACKGROUND: A single-dose dengue vaccine that protects individuals across a wide age range and regardless of dengue serostatus is an unmet need. We assessed the safety and efficacy of the live, attenuated, tetravalent Butantan-dengue vaccine (Butantan-DV) in adults, adolescents, and children. We previously reported the primary and secondary efficacy and safety endpoints in the initial 2 years of follow-up. Here we report the results through an extended follow-up period, with an average of 3·7 years of follow-up. METHODS: In this double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil, healthy participants (aged 2-59 years) who had not previously received a dengue vaccine were enrolled and randomly assigned 2:1 (stratified by age 18-59 years, 7-17 years, and 2-6 years) using a central electronic randomisation system to receive 0·5 mL of Butantan-DV (containing approximately 103 plaque-forming units of each of the four vaccine virus strains) or placebo, administered subcutaneously. Syringes containing vaccine or placebo were prepared by an unmasked trial pharmacist who was not involved in any subsequent participant assessments; other site staff and the participants remained unaware of the group allocations. Vaccine efficacy was calculated with the accrual of virologically confirmed dengue (VCD) cases (by RT-PCR) at least 28 days after vaccination up until the cutoff (at least 2 years of follow-up from the last participant enrolled). The primary endpoint was vaccine efficacy against VCD after day 28 by any dengue virus (DENV) serotype regardless of dengue serostatus at baseline in the per-protocol population. The primary and secondary safety endpoints up until day 21 were previously reported; secondary safety endpoints include the frequency of unsolicited vaccine-related adverse events after day 22. Safety analyses were done on all participants as treated. This trial is registered with ClinicalTrials.gov (NCT02406729) and is ongoing. FINDINGS: Of 16 363 participants assessed for eligibility, 16 235 were randomly assigned between Feb 22, 2016, and July 5, 2019, and received single-dose Butantan-DV (10 259 participants) or placebo (5976 participants). 16 162 participants (Butantan-DV n=10 215; placebo n=5947) were included in the per-protocol population and 16 235 (Butantan-DV n=10 259; placebo n=5976) in the safety population. At the data cutoff (July 13, 2021), participants had 2-5 years of follow-up (mean 3·7 years [SD 1·0], median 4·0 years [IQR 3·2-4·5]). 356 VCD cases were captured through the follow-up (128 in the vaccine group and 228 in the placebo group). Vaccine efficacy against VCD caused by any DENV serotype was 67·3% (95% CI 59·4-73·9); cases caused by DENV-3 or DENV-4 were not observed. The proportions of participants who had serious adverse events were similar between treatment groups (637 [6·2%] in the vaccine group and 395 [6·6%] in the placebo group) up until the cutoff. INTERPRETATION: A single dose of Butantan-DV was generally well tolerated and efficacious against symptomatic VCD (caused by DENV-1 and DENV-2) for a mean of 3·7 years. These findings support the continued development of Butantan-DV to prevent dengue disease in children, adolescents, and adults regardless of dengue serostatus. FUNDING: Instituto Butantan and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Increasing HIV screening in a secondary hospital emergency department in Brazil: searching for opportunities

Patients seeking emergency care have higher HIV prevalence than the general population, but HIV testing is often not offered in these settings, constituting missed opportunities for HIV testing. Semi structured interviews were conducted withemergency department health workers in a secondary hospital in Brazil. Interviews were recorded, transcribed, and analyzed for themes related to barriers and facilitator to HIV testing in emergency departments (EDs) and strategies to implement HIV screening programs. Currently, most providers reported only offering HIV testing when suspecting that the health problem that motivated the patient to seek care could be HIV-related. Although some providers believed that EDs would not be appropriate to implement screening programs, acceptability of HIV screening programs in this setting was overall high, particularly among nurses. Barriers to increasing HIV testing in EDs included concerns about time, understaffing, and increased costs. The initial triage was identified as a leverage point to obtain consent for HIV screening. Advantages and limitations of HIV screening programs at initial triage, testing blood samples collected for other reasons, and for patients undergoing emergency surgical procedures are discussed. EDs in medium income countries constitute a potential scenario to implement HIV screening programs, and such programs may benefit from empowering nursing staff to that end.

Los pacientes que acuden a urgencias presentan una prevalencia del VIH superior a la de la población general, pero a menudo no se ofrecen pruebas del VIH en estos entornos, lo que constituye una pérdida de oportunidades para realizarlas. Se realizaronentrevistas semiestructuradas a trabajadores sanitarios del servicio de urgencias de un hospital secundario de Brasil. Las entrevistas fueron grabadas, transcritas y analizadas en busca de temas relacionados con las barreras y los facilitadores de las pruebas del VIH en los servicios de urgencias (SU) y las estrategias para implementar programas de cribado del VIH. En la actualidad, la mayoría de los proveedores informaron que sólo ofrecen la prueba del VIH cuando sospechan que el problema de salud que motivó al paciente a buscar atención podría estar relacionado con el VIH. Aunque algunos proveedores creían que los SUH no serían apropiados para implementar programas de cribado, la aceptación de los programas de cribado del VIH en este entorno era en general alta, especialmente entre las enfermeras. Los obstáculos para aumentar las pruebas del VIH en los SUH incluían la preocupación por el tiempo, la falta de personal y el aumento de los costes. El triaje inicial se identificó como un punto de apoyo para obtener el consentimiento para el cribado del VIH. Se discuten las ventajas y limitaciones de los programas de cribado del VIH en el triaje inicial, el análisis de muestras de sangre recogidas por otras razones, y para los pacientes sometidos a procedimientos quirúrgicos de emergencia. Los SUH de países de renta media constituyen un escenario potencial para implementar programas de cribado del VIH, y dichos programas pueden beneficiarse de la capacitación del personal de enfermería para tal fin.

Os pacientes que procuram atendimento de emergência têm maior prevalência de HIV do que a população em geral, mas o teste de HIV muitas vezes não é oferecido nesses ambientes, o que constitui oportunidades perdidas para o teste de HIV. Foram realizadas entrevistas semiestruturadas com profissionais de saúde do departamento de emergência em um hospital secundário no Brasil. As entrevistas foram gravadas, transcritas e analisadas quanto a temas relacionados a barreiras e facilitadores do teste de HIV em departamentos de emergência (EDs) e estratégias para implementar programas de triagem de HIV. Atualmente, a maioria dos provedores relatou que só oferece testes de HIV quando suspeita que o problema de saúde que motivou o paciente a procurar atendimento pode estar relacionado ao HIV. Embora alguns provedores acreditassem que os departamentos de emergência não seriam apropriados para implementar programas de triagem, a aceitabilidade dos programas de triagem de HIV nesse ambiente foi, em geral, alta, especialmente entre os enfermeiros. As barreiras para aumentar os testes de HIV nos DEs incluíam preocupações com o tempo, falta de pessoal e aumento dos custos. A triagem inicial foi identificada como um ponto de alavancagem para obter o consentimento para a triagem de HIV. São discutidas as vantagens e as limitações dos programas de triagem de HIV na triagem inicial, no teste de amostras de sangue coletadas por outros motivos e para pacientes submetidos a procedimentos cirúrgicos de emergência. As salas de emergência em países de renda média constituem um cenário em potencial para a implementação de programas de triagem de HIV, e esses programas podem se beneficiar da capacitação da equipe de enfermagem para esse fim.

Missed opportunities for HIV diagnosis among incarcerated people in the Federal District, Brasilia, Brazil

Objective. Evaluate the pattern of contact with the healthcare system, including prison health facilities, and HIV testing. Method. This was a quantitative case-control study of HIV infected and uninfected incarcerated people serving time in 2019 in the Federal District, matched by age. Results. There was no difference in the pattern of contact with the healthcare system or the pattern of testing between HIV-infected and uninfected incarcerated people. Most of the infected patients were diagnosed in the prison environment and had early infections, demonstrating the effectiveness of screening in this scenario. Conclusion: The pattern of contact with the healthcare system among the individuals in this study probably reflects that of young men in general, i.e., less contact with primary care outpatient services and trauma as the main reason for contact in emergency departments. 

Objetivo. Evaluar el patrón de contacto con el sistema sanitario, incluidos los centros sanitarios penitenciarios, y las pruebas del VIH. Método. Estudio cuantitativo de casos y controles de personas infectadas y no infectadas por el VIH que cumplían condena en 2019 en el Distrito Federal, emparejadas por edad. Resultados. No hubo diferencias en el patrón de contacto con el sistema de salud ni en el patrón de realización de pruebas entre personas encarceladas infectadas y no infectadas por VIH. La mayoría de los pacientes infectados fueron diagnosticados en el medio penitenciario y presentaron infecciones precoces, lo que demuestra la eficacia del cribado en este escenario. Conclusiones. El patrón de contacto con el sistema sanitario entre los individuos de este estudio probablemente refleja el de los hombres jóvenes en general, es decir, menor contacto con los servicios ambulatorios de atención primaria y traumatismos como principal motivo de contacto en los servicios de urgencias. 

Objetivo. O estudo avaliou o padrão de contato com o sistema de saúde e de testagem para HIV, incluindo as unidades de saúde prisionais.  Métodos. Trata-se de estudo quantitativo de caso-controle em detentos que cumpriam pena em 2019 no Distrito Federal, pareados por idade. Resultados. Não houve diferença no padrão de contato com o sistema de saúde e padrão de oferta de testagem entre detentos infectados ou não com HIV. A maior parte dos infectados teve o diagnóstico realizado no ambiente prisional e de maneira precoce, evidenciando efetividade do rastreamento nesse cenário. Conclusão. O padrão de contato com o sistema de saúde dos indivíduos neste estudo reflete provavelmente o de homens jovens como um todo: pouco contato com serviços ambulatoriais de atenção primária e trauma como principal motivo de contato, em prontos-socorros.  

Live, Attenuated, Tetravalent Butantan-Dengue Vaccine in Children and Adults.

BACKGROUND: Butantan-Dengue Vaccine (Butantan-DV) is an investigational, single-dose, live, attenuated, tetravalent vaccine against dengue disease, but data on its overall efficacy are needed. METHODS: In an ongoing phase 3, double-blind trial in Brazil, we randomly assigned participants to receive Butantan-DV or placebo, with stratification according to age (2 to 6 years, 7 to 17 years, and 18 to 59 years); 5 years of follow-up is planned. The objectives of the trial were to evaluate overall vaccine efficacy against symptomatic, virologically confirmed dengue of any serotype occurring more than 28 days after vaccination (the primary efficacy end point), regardless of serostatus at baseline, and to describe safety up to day 21 (the primary safety end point). Here, vaccine efficacy was assessed on the basis of 2 years of follow-up for each participant, and safety as solicited vaccine-related adverse events reported up to day 21 after injection. Key secondary objectives were to assess vaccine efficacy among participants according to dengue serostatus at baseline and according to the dengue viral serotype; efficacy according to age was also assessed. RESULTS: Over a 3-year enrollment period, 16,235 participants received either Butantan-DV (10,259 participants) or placebo (5976 participants). The overall 2-year vaccine efficacy was 79.6% (95% confidence interval [CI], 70.0 to 86.3) - 73.6% (95% CI, 57.6 to 83.7) among participants with no evidence of previous dengue exposure and 89.2% (95% CI, 77.6 to 95.6) among those with a history of exposure. Vaccine efficacy was 80.1% (95% CI, 66.0 to 88.4) among participants 2 to 6 years of age, 77.8% (95% CI, 55.6 to 89.6) among those 7 to 17 years of age, and 90.0% (95% CI, 68.2 to 97.5) among those 18 to 59 years of age. Efficacy against DENV-1 was 89.5% (95% CI, 78.7 to 95.0) and against DENV-2 was 69.6% (95% CI, 50.8 to 81.5). DENV-3 and DENV-4 were not detected during the follow-up period. Solicited systemic vaccine- or placebo-related adverse events within 21 days after injection were more common with Butantan-DV than with placebo (58.3% of participants, vs. 45.6%). CONCLUSIONS: A single dose of Butantan-DV prevented symptomatic DENV-1 and DENV-2, regardless of dengue serostatus at baseline, through 2 years of follow-up. (Funded by Instituto Butantan and others; DEN-03-IB ClinicalTrials.gov number, NCT02406729, and WHO ICTRP number, U1111-1168-8679.).

Prevalence and Associated Factors of Post-COVID-19 Syndrome in a Brazilian Cohort after 3 and 6 Months of Hospital Discharge.

(1) Objectives: To evaluate the frequency and factors associated with the Post-COVID-19 Syndrome (PCS) in COVID-19 survivors after 3 and 6 months of hospital discharge; (2) Methods: We conducted a cohort study with patients who were hospitalized with COVID-19 in a referral public hospital in Brasília, Federal District, Brazil. After 3 and 6 months of discharge, patients answered a questionnaire about PCS symptoms. Poisson regression with robust variance was used to estimate the crude and adjusted prevalence ratios (PR and aPR) of PCS. (3) Results: The prevalence of PCS was 81% and 61% after 3 and 6 months of hospital discharge, respectively. The main symptoms after 3 months of discharge were hair loss (44%), fatigue (42%), and memory loss (39%); while after 6 months, they were memory loss (29%) and fatigue (27%). In the multivariate analysis, the main factor associated with PCS was female gender (aPR): 1.28 (1.16-1.41) and 1.60 (1.34-1.90), 3 and 6 months after hospital discharge, respectively. Hypercholesterolemia was also associated with PCS after 3 months aPR of 1.15 (1.04-1.27). After 6 months of discharge, obesity [aPR: 1.22 (1.03-1.45)] and pronation [aPR: 1.15 (1.06-1.25)] were relevant associated factors. (4) Conclusions: The prevalence of PCS was high in COVID-19 survivors who had the moderate and severe forms of the disease. Memory loss was the most persistent symptom. Our data pointed to female gender, hypercholesterolemia, obesity, and pronation during hospitalization as relevant PCS-associated risk factors.

The role of pets in SARS-CoV-2 transmission: an exploratory analysis.

PURPOSE: There is evidence that humans can transmit SARS-CoV-2 to cats and dogs. However, there is no evidence that they can transmit it back to humans or play any role in SARS-CoV-2 transmission. Here, we present an exploratory analysis on that matter. METHODS: We conducted a case-control study with participants with flu-like symptoms seeking care at a primary healthcare unit to be tested for COVID-19. They were asked if they owned pet cats and/or dogs in their residences, and this variable was evaluated as exposure. RESULTS: The odds ratio of "having dogs and/or cats in the residence" was 1.29 (95% CI 1.08-1.54) of "having only dogs and no cats" was 1.26 (1.05-1.52), and "no dogs and only cats" was 1.29 (0.95-1.75). CONCLUSION: Having a cat/dog in the house can affect the risk of infection by SARS-CoV-2.

SARS CoV-2 seroprevalence and diagnostic accuracy during a COVID-19 outbreak in a major penitentiary complex in Brazil, June to July 2020.

PURPOSE: This study aims to estimate the overall SARS-CoV-2 seroprevalence and evaluate the accuracy of an antibody rapid test compared to a reference serological assay during a COVID-19 outbreak in a prison complex housing over 13,000 prisoners in Brasília. DESIGN/METHODOLOGY/APPROACH: The authors obtained a randomized, stratified representative sample of each prison unit and conducted a repeated serosurvey among prisoners between June and July 2020, using a lateral-flow immunochromatographic assay (LFIA). Samples were also retested using a chemiluminescence enzyme immunoassay (CLIA) to compare SARS-CoV-2 seroprevalence and 21-days incidence, as well as to estimate the overall infection fatality rate (IFR) and determine the diagnostic accuracy of the LFIA test. FINDINGS: This study identified 485 eligible individuals and enrolled 460 participants. Baseline and 21-days follow-up seroprevalence were estimated at 52.0% (95% CI 44.9-59.0) and 56.7% (95% CI 48.2-65.3) with LFIA; and 80.7% (95% CI 74.1-87.3) and 81.1% (95% CI 74.4-87.8) with CLIA, with an overall IFR of 0.02%. There were 78.2% (95% CI 66.7-89.7) symptomatic individuals among the positive cases. Sensitivity and specificity of LFIA were estimated at 43.4% and 83.3% for IgM; 46.5% and 91.5% for IgG; and 59.1% and 77.3% for combined tests. ORIGINALITY/VALUE: The authors found high seroprevalence of anti-SARS-CoV-2 antibodies within the prison complex. The occurrence of asymptomatic infection highlights the importance of periodic mass testing in addition to case-finding of symptomatic individuals; however, the field performance of LFIA tests should be validated. This study recommends that vaccination strategies consider the inclusion of prisoners and prison staff in priority groups.

Informed consent for HIV screening in the emergency departments and human rights in patient care: seeking the right balance. / Consentimento informado para a testagem do HIV em unidades de pronto-socorro e direitos humanos dos pacientes: à procura de equilíbrio.

HIV exceptionalism refers to the fact that the illness is so different from other diseases that testing needs a special approach to informed consent. HIV infected people often visit health clinics, especially emergency departments, years before receiving a diagnosis without being tested for HIV. There is considerable public interest in increasing HIV testing in emergency departments. However, because these departments are sensitive environments that primarily provide urgent and emergency care, a number of ethical questions have been raised about the appropriateness of these settings for the implementation of universal screening programs. Human rights in patient care therefore constitutes an essential theoretical framework for analyzing ethical and legal dilemmas that arise in clinical encounters, thus strengthening the application of human rights principles to the context of patient care.

O "excepcionalismo" da infecção pelo HIV diz respeito ao fato de essa doença ser considerada tão diferente das demais e de que sua testagem necessita de uma abordagem especial em relação ao consentimento informado. Frequentemente, pessoas infectadas pelo HIV visitam unidades de assistência à saúde, sobretudo prontossocorros, anos antes de receberem um diagnóstico, sem terem sido testadas nessas oportunidades. Existe considerável interesse público em ampliar a testagem para o HIV em prontos-socorros. Por se tratar de ambiente sensível, cuja missão principal é o cuidado de urgências e emergências, há questionamentos quanto a esse ser um local apropriado para um programa de rastreamento universal, notadamente por questões éticas. Assim, os "direitos humanos dos pacientes" (DHP) constituem referencial teórico essencial para a análise de conflitos éticos que surgem no encontro clínico, fortalecendo a efetiva aplicação dos direitos humanos ao cuidado em saúde.

Frequency of exposure to arboviruses and characterization of Guillain Barré syndrome in a clinical cohort of patients treated at a tertiary referral center in Brasília, Federal District.

BACKGROUND: Guillian Barré syndrome (GBS) is an acute autoimmune polyradiculoneuropathy often associated with previous exposure to infectious agents. METHODS: A clinical cohort of 41 patients with GBS admitted to the Base Hospital Institute of the Federal District between May 2017 and April 2019 was followed up for 1 year. Serological tests for arbovirus detection and amplification of nucleic acids using polymerase chain reaction for zika virus (ZIKV), dengue virus (DENV), and chikungunya virus (CHIKV) were performed. RESULTS: The cohort consisted of 61% men with a median age of 40 years, and 83% had GBS-triggering events. A total of 54% had Grade 4 disability, 17% had Grade 3, 12% had Grade 2, 10% had Grade 5, and 7% had Grade 1. The classic form occurred in 83% of patients. Nerve conduction evaluations revealed acute demyelinating inflammatory polyneuropathy (51%), acute motor axonal neuropathy (17%), acute sensory-motor neuropathy (15%), and indeterminate forms (17%). Four patients were seropositive for DENV. There was no laboratory detection of ZIKV or CHIKV infection. Ninety percent of patients received human immunoglobulin. Intensive care unit admission occurred in 17.1% of the patients, and mechanical ventilation was used in 14.6%. One patient died of Bickerstaff's encephalitis. Most patients showed an improvement in disability at 10 weeks of follow-up. CONCLUSIONS: GBS in the Federal District showed a variable clinical spectrum, and it was possible to detect recent exposure to DENV.

Consentimento informado para a testagem do HIV em unidades de pronto-socorro e direitos humanos dos pacientes: à procura de equilíbrio / Informed consent for HIV screening in the emergency departments and human rights in patient care: seeking the right balance

Resumo O "excepcionalismo" da infecção pelo HIV diz respeito ao fato de essa doença ser considerada tão diferente das demais e de que sua testagem necessita de uma abordagem especial em relação ao consentimento informado. Frequentemente, pessoas infectadas pelo HIV visitam unidades de assistência à saúde, sobretudo prontossocorros, anos antes de receberem um diagnóstico, sem terem sido testadas nessas oportunidades. Existe considerável interesse público em ampliar a testagem para o HIV em prontos-socorros. Por se tratar de ambiente sensível, cuja missão principal é o cuidado de urgências e emergências, há questionamentos quanto a esse ser um local apropriado para um programa de rastreamento universal, notadamente por questões éticas. Assim, os "direitos humanos dos pacientes" (DHP) constituem referencial teórico essencial para a análise de conflitos éticos que surgem no encontro clínico, fortalecendo a efetiva aplicação dos direitos humanos ao cuidado em saúde.

Abstract HIV exceptionalism refers to the fact that the illness is so different from other diseases that testing needs a special approach to informed consent. HIV infected people often visit health clinics, especially emergency departments, years before receiving a diagnosis without being tested for HIV. There is considerable public interest in increasing HIV testing in emergency departments. However, because these departments are sensitive environments that primarily provide urgent and emergency care, a number of ethical questions have been raised about the appropriateness of these settings for the implementation of universal screening programs. Human rights in patient care therefore constitutes an essential theoretical framework for analyzing ethical and legal dilemmas that arise in clinical encounters, thus strengthening the application of human rights principles to the context of patient care.

Evidence of co-circulation of multiple arboviruses transmitted by Aedes species based on laboratory syndromic surveillance at a health unit in a slum of the Federal District, Brazil.

BACKGROUND: Vector-borne diseases, especially arboviruses transmitted by Aedes sp. mosquitos, should be a health policy priority in Brazil. Despite this urgency, there are significant limitations in the traditional surveillance system, mainly in vulnerable areas. This study aimed to investigate the circulation of dengue (DENV), Zika (ZIKV), and chikungunya viruses (CHIKV) by laboratory syndromic surveillance (LSS) in a slum area of the Federal District of Brazil, comparing the results with traditional surveillance data. METHODS: LSS for acute febrile and/or exanthematous symptoms was developed at a health unit of Cidade Estrutural, in order to identify the circulation of arboviruses transmitted by Aedes sp. mosquitos. Between June 2019 and March 2020, 131 valid participants were identified and sera tested by reverse transcription polymerase chain reaction (RT-PCR) for DENV (by serotype), ZIKV, and CHIKV acute infection and by immunoglobulin M enzyme-inked immunosorbent assay (ELISA-IgM) for DENV and CHIKV 15-21 days after symptom onset, when the participant reported no respiratory signs (cough and/or coryza). The results obtained were compared with traditional surveillance data for the study area and period. RESULTS: At least three DENV-1 (2.3%), four DENV-2 (3%), and one CHIKV (0.7%) cases were confirmed in the laboratory, showing evidence of hyperendemicity even though LSS had not reached the historic peak dengue fever months in the Federal District (April-May). When the results obtained here were compared with traditional surveillance, a significant discrepancy was observed, including underreporting of CHIKV infection. CONCLUSIONS: In addition to the risks posed to the study population, the area investigated with its respective socio-environmental profile may be a potential site for spread of the virus, given the cosmopolitan presence of Aedes sp. and human mobility in the Federal District. It is also suggested that traditional epidemiological surveillance may be reporting acute viral infections other than DENV as dengue fever, while underreporting other arboviruses transmitted by Aedes sp. mosquitos in the Federal District.

Neonatal healthcare-associated infections in Brazil: systematic review and meta-analysis.

BACKGROUND: Healthcare-associated infections (HAI) are important causes of neonatal morbidity and mortality in developing countries. We reviewed the incidence and the pathogens involved in HAI among infants admitted to neonatal intensive care units (NICU) in Brazil. METHODS: A search was conducted in the MEDLINE, LILACS and SciELO databases from January 1995 to October 2019. Two authors scrutinized potential articles independently, after one author selected them from screening abstracts from every article flagged as related to neonatal HAI. Then, they were included in the review if they met our inclusion criteria. The studies were evaluated based on a quality score proposed by the authors, rated 0 to 1, with 1 point as the best quality rate. Pooled estimates and 95% confidence intervals (95% CI) for HAI cumulative incidence and incidence density were calculated, when the same denominators were available, using meta-analysis. A quality effect was applied to the models using the MetaXL software. Heterogeneity was assessed using I2 statistics and the Cochran's Q test. RESULTS: Of a total of 5596 citations identified, 15 studies met the inclusion criteria for this review, which comprised 24,408 patients and 312,744 patient-days. Quality of the studies varied between 0.36 and 1 according to the adopted score, and six (40.0%) studies presented a score of 1. Pooled HAI incidence was 36.1 (95% CI 22.8-50.7) infections and 26.3 (95% CI 18.4-35.0) infected patients per 100 patients. Pooled HAI incidence density was 23.5 (95% CI 16.3-33.9) per 1000 patient-days. Pooled incidence density rates of bloodstream infection and ventilator-associated pneumonia were 13.1 per 1000 catheter-days (95% CI 4.3-40.1) and 7.9 per 1000 ventilator-days (95% CI 1.1-55.5), respectively. A high degree of heterogeneity was observed in all models (I2 > 98% and Cochran's Q test with p < 0.05). Coagulase-negative Staphylococci (32.1%), Staphylococcus aureus (13.8%) and Klebsiella spp. (12.4%) were the most prevalent causative bacterial pathogens. CONCLUSIONS: The findings show high incidence of neonatal HAI in Brazilian NICU; therefore, efforts to standardize the collection and notification of HAI are needed in order to strengthen surveillance in the country and implement preventive measures, routine assessment, and close monitoring of neonates.

Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial.

BACKGROUND: Steroid use for coronavirus disease 2019 (COVID-19) is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19. METHODS: A parallel, double-blind, placebo-controlled, randomized, Phase IIb clinical trial was performed with hospitalized patients aged ≥18 years with clinical, epidemiological, and/or radiological suspected COVID-19 at a tertiary care facility in Manaus, Brazil. Patients were randomly allocated (1:1 ratio) to receive either intravenous MP (0.5 mg/kg) or placebo (saline solution) twice daily for 5 days. A modified intention-to-treat (mITT) analysis was conducted. The primary outcome was 28-day mortality. RESULTS: From 18 April to 16 June 2020, 647 patients were screened, 416 were randomized, and 393 were analyzed as mITT, with 194 individuals assigned to MP and 199 to placebo. SARS-CoV-2 infection was confirmed by reverse transcriptase polymerase chain reaction in 81.3%. The mortality rates at Day 28 were not different between groups. A subgroup analysis showed that patients over 60 years old in the MP group had a lower mortality rate at Day 28. Patients in the MP arm tended to need more insulin therapy, and no difference was seen in virus clearance in respiratory secretion until Day 7. CONCLUSIONS: The findings of this study suggest that a short course of MP in hospitalized patients with COVID-19 did not reduce mortality in the overall population. CLINICAL TRIALS REGISTRATION: NCT04343729.

Visceral leishmaniasis lethality in Brazil: an exploratory analysis of associated demographic and socioeconomic factors.

INTRODUCTION: It is believed that delays in diagnosis and treatment of Visceral Leishmaniasis (VL) contribute significantly to the burden of VL lethality in Brazil. METHODS: This study included several parts: a descriptive cross-sectional study of the individual characteristics of deaths from disease; a descriptive ecological study of the spatial distribution of deaths from disease; and an ecological analytical study to evaluate the association between disease lethality rates and the demographic, socioeconomic, and health indicators. The study population comprised all cases diagnosed throughout the country per the National Disease Notification System (SINAN) and the total number of disease deaths recorded in the Mortality Information System (SIM) from 2007 to 2012. RESULTS: Of the 223 deaths from disease captured by pairing the databases, 59.1% were reported as "death from other causes". There were significant associations between VL lethality rate and municipalities with the highest proportion of vulnerable individuals (rate ratio (RR)=1.18, 95% confidence interval (CI): 1.01-1.27), with VL lower incidence rate (RR=0.62, 95% CI: 0.58-0.67) and a higher incidence rate of Acquired Immune Deficiency Syndrome (AIDS) (RR=1.20, 95% CI: 1.17-1.51). CONCLUSIONS: Linking the SINAN and SIM databases allowed the inclusion of 14% of otherwise underreported deaths from VL for the study period, showing that this method is useful for the surveillance of VL-related deaths. The size of the municipal population, proportion of the vulnerable population, incidence of disease, and the incidence of AIDS were associated with municipal lethality rates related to VL in Brazil.

Accuracy of diagnostic tests for American tegumentary leishmaniasis: a systematic literature review with meta-analyses.

OBJECTIVES: To analyse the accuracy of American tegumentary leishmaniasis (ATL) diagnostic methods and evaluate the quality of the existing publications by means of a systematic review. METHODS: Diagnostic tests evaluated in at least two studies with common reference standards were included in the sensitivity and/or specificity meta-analyses. Quality and susceptibility to bias were analysed using the QUADAS-2 and STARD tools. RESULTS: The title and abstract of 3387 publications were evaluated after deduplication resulting from database searches. Thirty-eight studies were included in the review, and 26 of them had results inserted in meta-analyses. The diagnostic methods with the highest pooled sensitivity values were ELISA, polymerase chain reaction (PCR), indirect immunofluorescence reaction and Montenegro's intradermal reaction. Cytometry was assessed in only two studies and presented 100% sensitivity in both. Smear slide microscopy and histopathology showed low pooled values of sensitivity. For specificity, the highest pooled values were identified for PCR. High values were also identified for ELISA, except for studies in which the reference standard for defining negative participants included individuals with Chagas' disease or paracoccidioidomycosis, which also occurred for cytometry. IFR had lower specificities than ELISA. There was a predominance of case-control designs of phase 1 or 2 and only four studies were strongly recommended as evidence generators. Several reference standards were adopted, and different methods were assessed in a small number of studies. CONCLUSION: PCR showed the highest accuracy for the diagnosis of ATL, and its use should be encouraged in clinical practice. ELISA is recommended for the screening of suspected individuals, but the possibility of cross-reactions should be considered. New validation studies for the tests evaluated in few publications and studies of phase 3 with appropriate methods are needed.

OBJECTIFS: Analyser l'exactitude des méthodes de diagnostic de la leishmaniose tégumentaire américaine (LTA) et évaluer la qualité des publications existantes au moyen d'une analyse systématique. MÉTHODES: Les tests diagnostiques évalués dans au moins deux études avec des étalons de référence communs ont été inclus dans les méta-analyses de sensibilité et/ou de spécificité. La qualité et la sensibilité au biais ont été analysées à l'aide des outils QUADAS-2 et STARD. RÉSULTATS: Le titre et le résumé de 3387 publications ont été évalués après déduplication résultant de recherches dans la base de données. 38 études ont été incluses dans la revue et 26 d'entre elles ont eu des résultats inclus dans des méta-analyses. Les méthodes de diagnostic avec les valeurs de sensibilité poolées les plus élevées étaient ELISA, la réaction en chaîne par polymérase (PCR), la réaction d'immunofluorescence indirecte et la réaction intradermique du Monténégro. La cytométrie a été évaluée dans seulement deux études et présentait une sensibilité de 100% dans les deux. La microscopie et l'histopathologie sur lame de frottis ont montré de faibles valeurs poolées de sensibilité. Pour la spécificité, les valeurs poolées les plus élevées ont été identifiées pour la PCR. Des valeurs élevées ont également été identifiées pour l'ELISA, à l'exception des études dans lesquelles la norme de référence pour définir les participants négatifs incluait des individus atteints de la maladie de Chagas ou de paracoccidioïdomycose, qui s'est également produite pour la cytométrie. L'IFR avait des spécificités plus faibles que l'ELISA. Il y avait une prédominance des essais cas-témoins de phases 1 ou 2 et seules quatre études étaient fortement recommandées comme génératrices de preuves. Plusieurs normes de référence ont été adoptées et différentes méthodes ont été évaluées dans un petit nombre d'études. CONCLUSION: la PCR a montré la plus grande exactitude pour le diagnostic de l'ATL et son utilisation doit être encouragée dans la pratique clinique. L'ELISA est recommandé pour le dépistage des personnes suspectées, mais la possibilité de réactions croisées doit être considérée. De nouvelles études de validation des tests évalués dans quelques publications et des études de phase 3 avec des méthodes appropriées sont nécessaires.

A cross-sectional approach including dog owner characteristics as predictors of visceral leishmaniasis infection in dogs.

BACKGROUND: Visceral leishmaniasis (VL) is relevant for human and animal public health. Several factors have been associated with the risk of Leishmania infantum infection in dogs. However, dog owner characteristics have been rarely explored. OBJECTIVES: To estimate the prevalence and to identify the associated factors for VL infection including dog owners characteristics. METHODS: A cross-sectional study was conducted including dogs from an endemic canine visceral leishmaniasis (CVL) region in the Federal District, Brazil. The infection was detected using parasitological, serological, and molecular methods. The associated factors were identified through Poisson regression modelling. FINDINGS: The prevalence of infection was 26.25% [95% confidence interval (CI): 20.05 to 33.57]. The associated factors were: short coat prevalence ratio (PR) = 2.33 (95% CI: 1.02 to 5.22); presence of backyard with predominance of soil and/or vegetation PR = 4.15 (95% CI: 1.35 to 12.77); and highest gross family income score PR = 2.03 (95% CI: 1.16 to 3.54). MAIN CONCLUSION: This is the first study that relates higher socioeconomic status of dog owners as an independent factor associated with higher prevalence of VL infection, along with other strongly associated factors related to receptive environment for phlebotomines. Our findings strengthen the need for exploration of the biological and behavioural bases linking dog owner characteristics to the risk of canine infection in prospective cohort studies.

Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial.

Importance: There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug. Objective: To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19. Design, Setting, and Participants: This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon. Interventions: Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days). Main Outcomes and Measures: Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4. Results: Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to high-dosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years) and more heart disease (5 of 28 [17.9%] vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%). Conclusions and Relevance: The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04323527.

HIV prevalence in recently incarcerated adult males in the Federal District, Brasilia, Brazil.

INTRODUCTION: This study intends to describe a HIV intake screening strategy in recently incarcerated adults in Distrito Federal, Brasilia, Brazil. METHODS: We tested 455 recently incarcerated adults in Distrito Federal in 2016 using rapid tests (RT) applied to oral samples (OS). RESULTS: The estimated frequency of positive tests was 0.88% (95% confidence interval [CI] 0.34% to 2.24%). CONCLUSIONS: The present findings reveal the potential significance of detecting new HIV infection cases in a vulnerable population using point-of-care rapid diagnostic tests.

A cross-sectional approach including dog owner characteristics as predictors of visceral leishmaniasis infection in dogs

BACKGROUND Visceral leishmaniasis (VL) is relevant for human and animal public health. Several factors have been associated with the risk of Leishmania infantum infection in dogs. However, dog owner characteristics have been rarely explored. OBJECTIVES To estimate the prevalence and to identify the associated factors for VL infection including dog owners characteristics. METHODS A cross-sectional study was conducted including dogs from an endemic canine visceral leishmaniasis (CVL) region in the Federal District, Brazil. The infection was detected using parasitological, serological, and molecular methods. The associated factors were identified through Poisson regression modelling. FINDINGS The prevalence of infection was 26.25% [95% confidence interval (CI): 20.05 to 33.57]. The associated factors were: short coat prevalence ratio (PR) = 2.33 (95% CI: 1.02 to 5.22); presence of backyard with predominance of soil and/or vegetation PR = 4.15 (95% CI: 1.35 to 12.77); and highest gross family income score PR = 2.03 (95% CI: 1.16 to 3.54). MAIN CONCLUSION This is the first study that relates higher socioeconomic status of dog owners as an independent factor associated with higher prevalence of VL infection, along with other strongly associated factors related to receptive environment for phlebotomines. Our findings strengthen the need for exploration of the biological and behavioural bases linking dog owner characteristics to the risk of canine infection in prospective cohort studies.