Effectiveness of mass dengue vaccination with CYD-TDV (Dengvaxia®) in the state of Paraná, Brazil: integrating case-cohort and case-control designs.

Background: CYD-TDV (Dengvaxia®) was the first dengue vaccine approved, launched in Brazil in 2015 for individuals aged 9-44 years. We aimed to estimate the effectiveness of CYD-TDV in preventing symptomatic dengue cases during a campaign targeting individuals aged 15-27 years in selected municipalities in Paraná, Brazil. Additionally, we examined whether a history of dengue, as recorded by the surveillance system, modified the vaccine's effectiveness. Methods: We conducted a case-cohort analysis comparing the frequency of vaccination, with at least one dose of CYD-TDV, in individuals with dengue confirmed by RT-PCR, identified by the surveillance system during 2019 and 2020, with the vaccination coverage in the target population. Moreover, in a case-control design using weighted controls, we assessed the documented history of dengue as a modifier of the vaccine's effectiveness. We used a logistic random-effects regression model, with data clustered in municipalities and incorporating covariates such as the incidence of dengue before the campaign, age, and sex. We calculated vaccine effectiveness (VE) as (1-relative risk) x 100%. Findings: 1869 dengue cases were identified, which had a vaccination frequency significantly lower than the overall vaccination coverage in the target population (50.3% vs. 57.2%, respectively; overall VE: 21.3%; 95% confidence interval [CI]: 13.4%-28.4%). In individuals with a documented history of dengue, vaccination had a VE of 71% (95% CI: 58%-80%) in reducing the incidence of dengue. However, vaccination was not associated with a significant reduction in the overall dengue case risk in individuals without a documented history of dengue (VE: 12%; 95% CI: -21% to 36%). In this last stratum, vaccination was associated with reduced cases due to DENV-1 and DENV-4, but an excess of DENV-2 cases. Interpretation: Vaccination led to a significant reduction in reported dengue cases within the target population. The case-control design suggested that this reduction was primarily driven by the benefits observed in individuals with a documented history of dengue. In endemic regions with limited serological testing facilities, a previous history of dengue diagnosis recorded by epidemiological surveillance could be used to triage candidates for CYD-TDV vaccination. Funding: Research supported by Sanofi.

Influenza A, like Omicron SARS-CoV-2, Is Similarly Detected in Saliva or Nasopharyngeal Samples via RT-qPCR.

After the Coronavirus pandemic, the importance of virus surveillance was highlighted, reinforcing the constant necessity of discussing and updating the methods for collection and diagnoses, including for other respiratory viruses. Although the nasopharyngeal swab is the gold-standard sample for detecting and genotyping SARS-CoV-2 and Influenza viruses, its collection is uncomfortable and requires specialized teams, which can be costly. During the pandemic, non-invasive saliva samples proved to be a suitable alternative for SARS-CoV-2 diagnosis, but for Influenza virus the use of this sample source is not recognized yet. In addition, most SARS-CoV-2 comparisons were conducted before the Omicron variant emerged. Here, we aimed to compare Influenza A and Omicron RT-qPCR analysis of nasopharyngeal swabs and saliva self-collection in paired samples from 663 individuals. We found that both nasopharyngeal swab and saliva collection are efficient for the diagnosis of Omicron (including sub-lineages) and for Influenza A, with high sensitivity and accuracy (>90%). The kappa index is 0.938 for Influenza A and 0.905 for SARS-CoV-2. These results showed excellent agreement between the two samples reinforcing saliva samples as a reliable source for detecting Omicron and highlighting saliva as a valid sample source for Influenza detection, considering this cheaper and more comfortable alternative.

Age Differences in Comorbidities, Presenting Symptoms, and Outcomes of Influenza Illness Requiring Hospitalization: A Worldwide Perspective From the Global Influenza Hospital Surveillance Network.

Background: The Global Influenza Hospital Surveillance Network (GIHSN) was established in 2012 to conduct coordinated worldwide influenza surveillance. In this study, we describe underlying comorbidities, symptoms, and outcomes in patients hospitalized with influenza. Methods: Between November 2018 and October 2019, GIHSN included 19 sites in 18 countries using a standardized surveillance protocol. Influenza infection was laboratory-confirmed with reverse-transcription polymerase chain reaction. A multivariate logistic regression model was utilized to analyze the extent to which various risk factors predict severe outcomes. Results: Of 16 022 enrolled patients, 21.9% had laboratory-confirmed influenza; 49.2% of influenza cases were A/H1N1pdm09. Fever and cough were the most common symptoms, although they decreased with age (P < .001). Shortness of breath was uncommon among those <50 years but increased with age (P < .001). Middle and older age and history of underlying diabetes or chronic obstructive pulmonary disease were associated with increased odds of death and intensive care unit (ICU) admission, and male sex and influenza vaccination were associated with lower odds. The ICU admissions and mortality occurred across the age spectrum. Conclusions: Both virus and host factors contributed to influenza burden. We identified age differences in comorbidities, presenting symptoms, and adverse clinical outcomes among those hospitalized with influenza and benefit from influenza vaccination in protecting against adverse clinical outcomes. The GIHSN provides an ongoing platform for global understanding of hospitalized influenza illness.

IgA antibody dynamics in healthcare workers after CoronaVac® vaccination and heterologous Comirnaty® booster dose.

BACKGROUND: This study is aimed at calculating the IgA antibody dynamic range in healthcare workers (HCWs) after immunization with CoronaVac® and Comirnaty® booster dose. METHODS: A total of 118 HCW serum samples from Southern Brazil were collected the day before the first vaccine dose (day 0) and + 20, + 40, + 110, + 200 days following the vaccine's first dose, and + 15 days after a Comirnaty® booster dose. Immunoglobulin A (IgA) was quantified using immunoassays for anti-S1 (spike) protein antibodies (Euroimmun, Lübeck, Germany). RESULTS: Seroconversion for the S1 protein occurred in 75 (63.56%) and 115 (97.47%) HCWs by day + 40 and day + 15 after the booster dose, respectively. There was an absence of IgA antibodies after the booster dose in two (1.69%) HCWs undergoing biannual rituximab administration and one (0.85%) HCW for no apparent reason. CONCLUSION: Complete vaccination showed a significant IgA antibody production response, and the booster dose considerably increased this response.

The Joint Initiative for Teaching and Learning on Global Health Challenges and One Health experience on implementing an online collaborative course.

The "Joint Initiative for Teaching and Learning on Global Health Challenges and One Health" piloted the online course "Global Health Challenges and One Health in 2021. The present work documents this experience, lessons learned, and the future outlook of the course. A descriptive study was conducted based on the evaluations performed with the enrolled students and course coordinators. Of 30 enrolled students from graduate programs of six institutions from Brazil, Germany, Mozambique, and Kosovo, two unenrolled, and nine failed for not completing the activities. Therefore, 19 (63%) students completed the course. Some challenges identified were language and technology access barriers, difficulty scheduling group meetings due to different time zones, and high workload per credit in some institutions. Activities in groups conducted synchronously, such as debates, journal clubs, and case studies, were highlighted as those with higher impact in the learning process, having more participation of students when carried in small groups. Some students reported the establishment of research and work partnerships with other participants from partner institutions. The experience reinforces the importance of international exchange to improve collaboration between institutions and the impact of working in small interprofessional groups to develop technical, intercultural, and interdisciplinarity competencies necessary to human resources working with the One Health approach. The success of such international educational initiatives depends on overcoming barriers to implementation, which can be detected in institutional and course levels. Therefore, continuing evaluation of the course and improvements must be performed and involve all participants.

Antibody response following a Comirnaty booster dose in CoronaVac vaccinated individuals.

Serum samples from 106 health care workers were analyzed by enzyme-linked immunosorbent assay (ELISA) test 15 days after a booster dose. A total of 99% of the participants showed a significant increase in the anti-S1 IgG index. The significant humoral response was observed 15 days after the heterologous dose of Comirnaty in most the subjects, regardless of having comorbidities. The administration of a third booster dose is suggested 5 months after the second vaccine dose of the initial vaccine.

HIV, syphilis, hepatitis B and C in key populations: results of a 10-year cross-sectional study, Southern Brazil.

OBJECTIVE: Although the development of prevention and treatment strategies for sexually transmitted infections in key groups has improved over the years, they still remain a challenge for health systems worldwide. In this context, the objective of this study is to assess the seroprevalence in the tested population, with an emphasis on key populations, aiming at identifying the participants' profile and consequently the development of testing strategies. METHODS: The present study analyzed the seroprevalence of HIV, syphilis, and hepatitis B and C, and the epidemiological profiles of key and general populations tested at a reference public health facility for sexually transmitted infections testing and counseling in the city of Curitiba, Southern Brazil. A cross-sectional study was conducted to report data from 2010 to 2019. RESULTS: A total of 67,448 samples were analyzed, 9,086 of these tested positive, 3,633 (56%) for HIV, 4,978 (77%) for syphilis, 340 (5%) for hepatitis C virus (HCV), and 135 (2%) for hepatitis B virus (HBV). Overall, most of the participants were men (79 to 87%), and predominantly white. For HIV and syphilis, the predominant age groups were 21-30 years old (48 and 50%), HBV 21-40 years old (31%), and HCV 41-60 years old (25%). A high seroprevalence of HIV and syphilis was observed in the investigated key populations with a higher frequency in sex workers, men who have sex with men, and transgender. CONCLUSION: The progressive increase in syphilis cases emphasizes the need for effective interventions to enhance adherence to the use of condoms, and to expand diagnosis and treatment for these key populations.

SARS-CoV-2 Delta and Omicron Variants Surge in Curitiba, Southern Brazil, and Its Impact on Overall COVID-19 Lethality.

Screening efforts and genomic surveillance are essential tools to evaluate the course of the COVID-19 pandemic and assist the public healthcare system in dealing with an increasing number of infections. For the analysis of COVID-19 cases scenarios in Curitiba, Paraná, Brazil, we performed a diagnosis of positive cases, coupled with genotyping, for symptomatic and asymptomatic members of the Federal University of Paraná. We achieved over 1000 samples using RT-qPCR for diagnosis. The posterior genotyping allowed us to observe differences in the spread of strains in Curitiba, Brazil. The Delta variant was not associated with an infection wave, whereas the rapid Omicron variant spread became dominant in less than one month. We also evaluated the general vaccination coverage in the state, observing a striking reduction in lethality correlated to the vaccinated fraction of the population; although lower lethality rates were not much affected by the Omicron variant wave, the same effect was not translated in the number of infections. In summary, our results provide a general overview of the pandemic's course in Paraná State and how there was reduction in lethality after a combination of multiple infection waves and a large-scale vaccination program.

Comparison of SARS-CoV-2 molecular detection in nasopharyngeal swab, saliva, and gargle samples.

The nasopharyngeal swab is a gold standard for detecting SARS-CoV-2. However, the inconvenience of this method compelled us to compare its efficiency with saliva and gargle samples, which we collected sequentially from 229 individuals. Saliva outperformed gargle samples, constituting a reliable RNA viral source with similar performance to nasopharyngeal samples.

Severe acute respiratory syndrome coronavirus 2 infection among healthcare workers in a tertiary public hospital in Curitiba, Brazil.

BACKGROUND: We aimed to describe the clinical characteristics of coronavirus disease 2019 (COVID-19) among healthcare workers (HCWs) in Curitiba, Brazil. METHODS: Upper respiratory samples from 1077 HCWs were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using reverse transcription polymerase chain reaction from June 16, 2020 to December 9, 2020. RESULTS: Overall, 32.7% of HCWs were infected. The positivity rates in symptomatic and asymptomatic HCWs were 39.2% and 15.9%, respectively. Hospital departments categorized as high-risk for exposure had the highest number of infected HCWs. CONCLUSIONS: Early diagnosis and isolation of infected HCWs remain key in controlling SARS-CoV-2 transmission because HCWs in close contact with COVID-19 patients are more likely to be infected than those who are not.

The association of breastfeeding and other factors on respiratory virus positivity and severity in hospitalized children.

Acute respiratory infections (ARIs) are the most prevalent diseases in children under 5 years old, and viruses are the leading cause. ARIs arise due to numerous factors, including age, contact with siblings or other children in daycare centers, and environmental pollution. Breastfeeding reportedly confers protection against ARIs through bioactive components related to mucous epithelial immunity. This study aimed to evaluate the frequency and severity of viral ARIs in hospitalized children, together with the status and duration of exclusive breastfeeding (EBF) and other associated factors. It comprised an epidemiological surveillance study to investigate respiratory viruses in hospitalized children, in which demographic and clinical data were collected. Overall, 279 patients were included, 190 (68%) had positive viral results, and 132 (47%) were exclusively breastfed. In an adjusted analysis, it was observed that older children, the parents' educational level, and the presence of chronic disease were significantly related to EBF for more than 6 months. No significant differences were observed in viral positivity and disease severity concerning EBF. Whereas the EBF status was associated with a positive rate of virus detection, the significance did not remain after adjustment, and it was not considered a protective factor against ARIs. On the other hand, young age and exposure to tobacco were confirmed as risk factors of frequency and severity, respectively. Such confounding factors can impact the analysis and should be considered in future studies.

Dynamic of humoral response to SARS-CoV-2 anti-Nucleocapsid and Spike proteins after CoronaVac vaccination.

This study aimed to calculate the seroconversion rate and IgG antibody dynamic range of the CoronaVac vaccine in healthcare workers (HCWs) after immunization. Serum samples from 133 HCWs from Southern Brazil were collected 1 day before (Day 0) and +10, +20, +40, + 60, +110 days after administering the vaccine's first dose. Immunoglobulin G (IgG) was quantified using immunoassays for anti-N-protein (nucleocapsid) antibodies (Abbott, Sligo, Ireland) and for anti-S1 (spike) protein antibodies (Euroimmun, Lübeck, Germany). Seroconversion by day 40 occurred in 129 (97%) HCWs for the S1 protein, and in 69 (51.87%) HCWs for the N protein. An absence of IgG antibodies (by both methodologies), occurred in 2 (1.5%) HCWs undergoing semiannual rituximab administration, and also in another 2 (1.5%) HCWs with no apparent reason. This study showed that CoronaVac has a high seroconversion rate when evaluated in an HCW population.

HIV, syphilis, hepatitis B and C in key populations: results of a 10-year cross-sectional study, Southern Brazil

ABSTRACT Objective: Although the development of prevention and treatment strategies for sexually transmitted infections in key groups has improved over the years, they still remain a challenge for health systems worldwide. In this context, the objective of this study is to assess the seroprevalence in the tested population, with an emphasis on key populations, aiming at identifying the participants' profile and consequently the development of testing strategies. Methods: The present study analyzed the seroprevalence of HIV, syphilis, and hepatitis B and C, and the epidemiological profiles of key and general populations tested at a reference public health facility for sexually transmitted infections testing and counseling in the city of Curitiba, Southern Brazil. A cross-sectional study was conducted to report data from 2010 to 2019. Results: A total of 67,448 samples were analyzed, 9,086 of these tested positive, 3,633 (56%) for HIV, 4,978 (77%) for syphilis, 340 (5%) for hepatitis C virus (HCV), and 135 (2%) for hepatitis B virus (HBV). Overall, most of the participants were men (79 to 87%), and predominantly white. For HIV and syphilis, the predominant age groups were 21-30 years old (48 and 50%), HBV 21-40 years old (31%), and HCV 41-60 years old (25%). A high seroprevalence of HIV and syphilis was observed in the investigated key populations with a higher frequency in sex workers, men who have sex with men, and transgender. Conclusion: The progressive increase in syphilis cases emphasizes the need for effective interventions to enhance adherence to the use of condoms, and to expand diagnosis and treatment for these key populations.

Severe acute respiratory syndrome coronavirus 2 infection among healthcare workers in a tertiary public hospital in Curitiba, Brazil

ABSTRACT BACKGROUND: We aimed to describe the clinical characteristics of coronavirus disease 2019 (COVID-19) among healthcare workers (HCWs) in Curitiba, Brazil. METHODS: Upper respiratory samples from 1077 HCWs were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using reverse transcription polymerase chain reaction from June 16, 2020 to December 9, 2020. RESULTS: Overall, 32.7% of HCWs were infected. The positivity rates in symptomatic and asymptomatic HCWs were 39.2% and 15.9%, respectively. Hospital departments categorized as high-risk for exposure had the highest number of infected HCWs. CONCLUSIONS: Early diagnosis and isolation of infected HCWs remain key in controlling SARS-CoV-2 transmission because HCWs in close contact with COVID-19 patients are more likely to be infected than those who are not.

Large-Scale Screening of Asymptomatic Persons for SARS-CoV-2 Variants of Concern and Gamma Takeover, Brazil.

We performed a large-scale severe acute respiratory syndrome coronavirus 2 screening campaign using 2 PCR-based approaches, coupled with variant genotyping, aiming to provide a safer environment for employees of Federal University in Curitiba, Brazil. We observed the rapid spread of the Gamma variant of concern, which replaced other variants in <3 months.

NEAT1 and MALAT1 are highly expressed in saliva and nasopharyngeal swab samples of COVID-19 patients.

COVID-19, caused by the SARS-CoV-2 virus, has become a significant global public health problem, with a wide variety of clinical manifestations and disease progression outcomes. LncRNAs are key regulators of the immune response and have been associated with COVID-19 risk infection. Previous studies focused mainly on in-silico analysis of lncRNA expression in the lungs or peripheral blood cells. We evaluated the expression of lncRNAs NEAT1, MALAT1, and MIR3142 in saliva and nasopharyngeal swab from SARS-CoV-2 positive (n = 34) and negative patients (n = 46). A higher expression of the lncRNAs NEAT1 and MALAT1 (p < 0.05) were found in positive samples. NEAT1 had a higher expression mainly in saliva samples (p < 0.001), and MALAT1 was upregulated in nasopharyngeal samples (p < 0.05). Area under the ROC curve for NEAT1 in saliva was 0.8067. This study was the first to investigate the expression of lncRNAs in saliva and nasopharyngeal samples of COVID-19 patients, which gives new insights into the initial response to infection and infectivity and may provide new biomarkers for severity and targets for therapy.

Association Between COVID-19 Pregnant Women Symptoms Severity and Placental Morphologic Features.

Since the beginning of the pandemic, few papers describe the placenta's morphological and morphometrical features in SARS-CoV-2-positive pregnant women. Alterations, such as low placental weight, accelerated villous maturation, decidual vasculopathy, infarcts, thrombosis of fetal placental vessels, and chronic histiocytic intervillositis (CHI), have been described. Objective: To analyze clinical data and the placental morphological and morphometric changes of pregnant women infected with SARS-CoV-2 (COVID-19 group) in comparison with the placentas of non-infected pregnant women, matched for maternal age and comorbidities, besides gestational age of delivery (Control group). Method: The patients in the COVID-19 and the Control group were matched for maternal age, gestational age, and comorbidities. The morphological analysis of placentas was performed using Amsterdam Placental Workshop Group Consensus Statement. The quantitative morphometric evaluation included perimeter diameter and number of tertiary villi, number of sprouts and knots, evaluation of deposition of villous fibrin, and deposition of intra-villous collagen I and III by Sirius Red. Additionally, Hofbauer cells (HC) were counted within villi by immunohistochemistry with CD68 marker. Results: Compared to controls, symptomatic women in the COVID-19 group were more likely to have at least one comorbidity, to evolve to preterm labor and infant death, and to have positive SARS-CoV-2 RNA testing in their concepts. Compared to controls, placentas in the COVID-19 group were more likely to show features of maternal and fetal vascular malperfusion. In the COVID-19 group, placentas of symptomatic women were more likely to show CHI. No significant results were found after morphometric analysis. Conclusion: Pregnant women with symptomatic SARS-CoV-2 infection, particularly with the severe course, are more likely to exhibit an adverse fetal outcome, with slightly more frequent histopathologic findings of maternal and fetal vascular malperfusion, and CHI. The morphometric changes found in the placentas of the COVID-19 group do not seem to be different from those observed in the Control group, as far as maternal age, gestational age, and comorbidities are paired. Only the deposition of villous fibrin could be more accentuated in the COVID-19 group (p = 0.08 borderline). The number of HC/villous evaluated with CD68 immunohistochemistry did not show a difference between both groups.

Care management in coping with COVID-19 at a teaching hospital.

OBJECTIVE: to report the experience of implementing care management strategies in coping with the COVID-19 pandemic in a teaching hospital. METHOD: this is an experience report of the managers who work at the largest public hospital in Paraná with functions as Head of the Care Management Division, Head of the Care Lines Management Sector, Head of the Infectiology Unit and support team. RESULTS: care management strategies were structured based on the service dynamics; physical structure; human Resources; professional and user safety. FINAL CONSIDERATIONS: preparing for a pandemic involves measures that include modifying infrastructure and processes, managing employees and users, infection prevention strategies, and clinical recommendations. These measures are necessary to optimize the quality of care provided to users with COVID-19 and to reduce the risk of viral transmission to other users or health professionals.

SARS-CoV-2 in asymptomatic pregnant women in South Brazil: RT-PCR and serological detection.

OBJECTIVES: This study aims to detect the SARS-CoV-2 infection prevalence in asymptomatic pregnant women. METHODS: A group of 195 asymptomatic pregnant women who attended the prenatal care outclinic and to the obstetric emergency department was tested concomitantly for SARS-CoV-2 by RT-PCR and serological tests. RESULTS: The virus was detected by RT-PCR in two (1.02%) cases and 17 (8.71%) patients had antibodies detected by immunochromatographic tests. CONCLUSIONS: Due to the high risk of this emerging infection in the health of pregnant women, fetuses and newborns, we suggest the universal screening of all pregnant women admitted to hospital through the combined method RT-PCR and serological.

Simultaneous enterovirus EV-D68 and CVA6 infections causing acute respiratory distress syndrome and hand, foot and mouth disease.

BACKGROUND: Although most enterovirus (EV) infections can be asymptomatic, these viral agents can cause serious conditions associated with central nervous system, respiratory disease and uncommon manifestations of hand, foot and mouth disease (HFMD). EV-coinfections have been rarely reported with development of complications and severe clinical outcome. An atypical case of a child presenting HFMD and severe acute respiratory syndrome, co-infected with EV-D68 and CVA6, is reported herein. CASE PRESENTATION: A 3-year-old boy was admitted in the emergency department unit showing fever, abdominal pain and tachycardia. Twenty-four hours after hospitalization the child developed severe clinical symptoms associated with HFMD and was discharged after recovery. Two days later, the child was readmitted with fever, cough and respiratory distress. RT-PCR and Sanger sequencing confirmed positivity for EV-D68 and CVA6 in oro and nasopharynges swabs and vesicles fluid, respectively. Phylogenetic analysis based on VP1 gene sequences suggested that CVA6 was closely related with HFMD viruses circulating in Turkey, while EV-D68 was genetically related to a Chinese strain. CONCLUSIONS: To the best of our knowledge, this case is the first report of a double infection caused by CVA6 and EV-D68, which shed light on the pathogenesis of enterovirus infections. Further studies must be conducted to ascertain the role and clinical significance of EV co-infections, as well as a potential synergistic pathway between these viruses.