Immune response induced by standard and fractional doses of 17DD yellow fever vaccine.

The re-emergence of yellow fever (YF) urged new mass vaccination campaigns and, in 2017, the World Health Organization approved the use of the fractional dose (FD) of the YF vaccine due to stock shortage. In an observational cross-sectional investigation, we have assessed viremia, antibodies, soluble mediators and effector and memory T and B-cells induced by primary vaccination of volunteers with FD and standard dose (SD). Similar viremia and levels of antibodies and soluble markers were induced early after immunization. However, a faster decrease in the latter was observed after SD. The FD led to a sustained expansion of helper T-cells and an increased expression of activation markers on T-cells early after vaccination. Although with different kinetics, expansion of plasma cells was induced upon SD and FD immunization. Integrative analysis reveals that FD induces a more complex network involving follicular helper T cells and B-cells than SD. Our findings substantiate that FD can replace SD inducing robust correlates of protective immune response against YF.

Yellow Fever Vaccine-Associated Viscerotropic Disease among Siblings, São Paulo State, Brazil.

We describe 5 cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) in 2 familial clusters during the 2017-2018 yellow fever (YF) vaccination campaign in São Paulo state, Brazil. The first case was that of a 40-year-old white man who died of icterohemorrhagic syndrome, which was confirmed to be YEL-AVD by using real-time reverse transcription PCR to detect 17DD YF vaccine in the liver. Ten years previously, his brother died of a clinically similar disease without a confirmed diagnosis 9 days after YF vaccination. The second cluster included 3 of 9 siblings in whom hepatitis developed in the first week after receiving fractionated doses of YF vaccine. Two of them died of hemorrhagic diathesis and renal and respiratory failure, and 17DD-YF vaccine was detected in serum samples from all patients and in the liver in 1 case. Genetic factors might play a substantial role in the incidence of YEL-AVD.

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in inadvertently vaccinated healthy children.

Twenty-seven children aged seven months to 5 years were inadvertently vaccinated with a COVID-19 vaccine, the CoronaVac (Sinovac, China), an inactivated SARS-CoV-2 vaccine, in two different cities of Sao Paulo State, Brazil. After the event, these children were monitored by local pediatricians and serum samples were collected at the first visit and 30 days after vaccination and tested for SARS-CoV-2 S1 serology with Ortho total IgG anti-S1 protein and Cpass, an ACE2 receptor binding domain inhibition assay. Only one child had a mild symptom after vaccination, with no other adverse events documented up to the 30 days follow-up. Of 27 children tested 3-9 days after vaccination, 5 (19%) had positive serology suggesting a previous natural SARS-CoV-2 infection, with all 19 tested on day 30 after vaccination and presenting with positive tests, with an increment of antibody titers in those initially positive. A low Cpass binding inhibition was observed in the first collection in 11 seronegative cases, with high titers among those anti-S1 positive. All children showed an important increase in antibody titers on day 30. The event allowed the documentation of a robust serological response to one dose of CoronaVac in this small population of young children, with no major adverse effects. Although it was an unfortunate accident, this event may contribute with future vaccine strategies in this age group. The data suggest that CoronaVac is safe and immunogenic for children.

Risk Factors for Death Among 120,804 Hospitalized Patients with Confirmed COVID-19 in São Paulo, Brazil.

São Paulo is a state in Brazil with one of the highest numbers of confirmed and severe cases of coronavirus disease (COVID-19), with an incidence of 294 hospitalizations per 100,000 inhabitants. We report the clinical characteristics and outcomes of 120,804 hospitalized patients with confirmed COVID-19 from February 26 to October 10, 2020, in São Paulo. Characteristics of patients who died and survived were compared using a survival analysis. The median age was 60 years (interquartile range [IQR], 47-72), 67,821 (56.1%) were men, and 61,659 (51.0%) were white. Most hospitalized patients (79,812; 66.1%) reported one or more comorbidities, 41,708 (34.5%) hospitalized patients were admitted to intensive care units, and 33,079 (27.4%) died. Men (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.18-1.25), elderly individuals (HR, 3.85; 95% CI, 3.68-4.02), and patients with chronic cardiovascular disease including hypertension (HR, 1.05; 95% CI, 1.02-1.08), chronic lung disease (HR, 1.38; 95% CI, 1.31-1.45), diabetes mellitus (HR, 1.14; 95% CI, 1.11-1.18), and chronic neurological disease (HR, 1.48; 95% CI, 1.41-1.55) were at higher risk for death from COVID-19.

Risk Factors for Death Among 120,804 Hospitalized Patients with Confirmed COVID-19 in São Paulo, Brazil

São Paulo is a state in Brazil with one of the highest numbers of confirmed and severe cases of coronavirus disease (COVID-19), with an incidence of 294 hospitalizations per 100,000 inhabitants. We report the clinical characteristics and outcomes of 120,804 hospitalized patients with confirmed COVID-19 from February 26 to October 10, 2020, in São Paulo. Characteristics of patients who died and survived were compared using a survival analysis. The median age was 60 years (interquartile range [IQR], 47­72), 67,821 (56.1%) were men, and 61,659 (51.0%) were white. Most hospitalized patients (79,812; 66.1%) reported one or more comorbidities, 41,708 (34.5%) hospitalized patients were admitted to intensive care units, and 33,079 (27.4%) died. Men (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.18­1.25), elderly individuals (HR, 3.85; 95% CI, 3.68­4.02), and patients with chronic cardiovascular disease including hypertension (HR, 1.05; 95% CI, 1.02­1.08), chronic lung disease (HR, 1.38; 95% CI, 1.31­1.45), diabetes mellitus (HR, 1.14; 95% CI, 1.11­1.18), and chronic neurological disease (HR, 1.48; 95% CI, 1.41­1.55) were at higher risk for death from COVID-19.

The search for yellow fever virus vaccine in breast milk of inadvertently vaccinated women in Brazil.

Eleven lactating women were inadvertently vaccinated with 17DD yellow fever vaccine in a small city of Sao Paulo State, Brazil. Their infants were being exclusively breast-fed and the breastfeeding was interrupted for 10 days. Serum and breastmilk were collected from the vaccinated mothers and tested for the presence of genomic RNA of the vaccine strain 8, 10 and 15 days after vaccination. Viral RNA was not detected in any of the serum and human milk samples tested and the infants remained asymptomatic. Our result strengthens the effectineness of stopping breastfeeding for 10 days after the inadvertent yellow fever vaccination of lactating women.

Occurrence of hepatitis B in pregnant women and follow-up of exposed children in the State of São Paulo, Brazil, in 2012. / Ocorrência de hepatite B em gestantes e seguimento de crianças expostas no estado de São Paulo, em 2012.

OBJECTIVE: to describe the occurrence of hepatitis B among pregnant women, immunoprophylaxis and vertical and perinatal transmission in children exposed to the virus in the São Paulo state primary care network, Brazil. METHODS: this was a cross-sectional study using prenatal records of pregnant women attending health services between January and June 2012 and a cohort of newborns; the frequencies of the results were described and the estimated occurrence of hepatitis B was calculated. RESULTS: 6,233 pregnant women were included, of whom 53.1% were between 20-29 years old, 58.7% had 8-11 years of schooling, 53.3% were white, and 73.9% lived with a partner; occurrence of hepatitis B was 0.13% (95%CI 0.04; 0.21); of the eight children of mothers with chronic hepatitis B, six had a complete vaccination schedule, and there was no vertical or perinatal transmission. CONCLUSION: there was low occurrence of hepatitis B in pregnant women and absence of vertical or perinatal transmission.

Outbreak investigation in cargo ship in times of COVID-19 crisis, Port of Santos, Brazil.

In February 2020, a Chinese cargo ship docked at the Port of Santos with reports of crew members with a feverish and respiratory condition. A team was gathered to verify the existence of suspected cases of COVID-19 inside the vessel and define its clearance. All 25 crew members were interviewed, and no suspected cases were found. The vessel was then cleared for port activities. The investigation resulted from the implementation of the contingency plan to face a public health emergency of international importance and several surveillance entities cooperated.

Outbreak investigation in cargo ship in times of COVID-19 crisis, Port of Santos, Brazil / Investigação de surto em navio de carga em tempo de COVID-19, Porto de Santos, Brasil

ABSTRACT In February 2020, a Chinese cargo ship docked at the Port of Santos with reports of crew members with a feverish and respiratory condition. A team was gathered to verify the existence of suspected cases of COVID-19 inside the vessel and define its clearance. All 25 crew members were interviewed, and no suspected cases were found. The vessel was then cleared for port activities. The investigation resulted from the implementation of the contingency plan to face a public health emergency of international importance and several surveillance entities cooperated.

RESUMO Em fevereiro de 2020, um navio de carga vindo da China atracou no Porto de Santos com relato de tripulantes com quadro febril e respiratório. Uma equipe foi mobilizada para verificar a existência de casos suspeitos de COVID-19 dentro da embarcação e definir a liberação da embarcação no porto. Todos os 25 tripulantes foram entrevistados e não foram encontrados casos suspeitos. Então a embarcação foi liberada para atividades no porto. A investigação resultou da aplicação do plano de contingência diante de uma emergência de saúde pública de importância internacional e houve a colaboração de diversas entidades de vigilância.

Outbreak investigation in cargo ship in times of COVID-19 crisis, Port of Santos, Brazil

In February 2020, a Chinese cargo ship docked at the Port of Santos with reports of crew members with a feverish and respiratory condition. A team was gathered to verify the existence of suspected cases of COVID-19 inside the vessel and define its clearance. All 25 crew members were interviewed, and no suspected cases were found. The vessel was then cleared for port activities. The investigation resulted from the implementation of the contingency plan to face a public health emergency of international importance and several surveillance entities cooperated. DESCRIPTORS: Coronavirus Infections, epidemiology. Coronavirus Infections, prevention & control. Ships. International Health Regulations.

Ocorrência de hepatite B em gestantes e seguimento de crianças expostas no estado de São Paulo, em 2012 / Ocurrencia de hepatitis B en mujeres embarazadas y seguimiento de niños expuestos en el estado de São Paulo, Brasil, en 2012 / Occurrence of hepatitis B in pregnant women and follow-up of exposed children in the State of São Paulo, Brazil, in 2012

Resumo Objetivo: descrever a ocorrência da hepatite B entre gestantes, a realização de imunoprofilaxia e a transmissão vertical e perinatal nas crianças expostas ao vírus na rede de Atenção Primária à Saúde do estado de São Paulo, Brasil. Métodos: estudo transversal sobre registros de pré-natal de gestantes atendidas de janeiro a junho de 2012 e coorte dos recém-nascidos; foram descritas as frequências dos resultados e calculada a estimativa da ocorrência da hepatite B. Resultados: foram incluídas 6.233 gestantes, das quais 53,1% com 20 a 29 anos de idade, 58,7% com 8 a 11 anos de estudo, 53,3% brancas e 73,9% com companheiro; a ocorrência de hepatite B foi de 0,13% (IC95%: 0,04 a 0,21%); das oito crianças de mães com hepatite B crônica, seis tiveram esquema vacinal completo e não houve transmissão vertical ou perinatal. Conclusão: observou-se baixa ocorrência de hepatite B em gestantes e ausência de transmissão vertical ou perinatal.

Resumen Objetivo: describir el aparecimiento de hepatitis B en mujeres embarazadas, la inmunoprofilaxis y la transmisión vertical y perinatal en niños expuestos al virus en la red de atención primaria en el estado de São Paulo, Brasil. Métodos: estudio transversal con registros prenatales de mujeres embarazadas atendidas de enero a junio de 2012 y cohorte de recién nacidos; se describieron las frecuencias y se calculó el surgimiento de la hepatitis B. Resultados: se incluyeron 6.233 gestantes, de las cuales 53,1% con 20 a 29 años de edad, 58,7% con 8 a 11 años de estudios, 53,3% blancas y 73,9% viviendo en pareja; la ocurrencia de hepatitis B fue del 0,13% (IC95%: 0,04 to 0,21%); entre ocho hijos de madres con hepatitis B crónica, seis tenía un calendario de vacunación completo y no había transmisión vertical o perinatal. Conclusión: hubo baja ocurrencia de hepatitis B en mujeres embarazadas y ausencia de transmisión vertical o perinatal.

Abstract Objective: to describe the occurrence of hepatitis B among pregnant women, immunoprophylaxis and vertical and perinatal transmission in children exposed to the virus in the São Paulo state primary care network, Brazil. Methods: this was a cross-sectional study using prenatal records of pregnant women attending health services between January and June 2012 and a cohort of newborns; the frequencies of the results were described and the estimated occurrence of hepatitis B was calculated. Results: 6,233 pregnant women were included, of whom 53.1% were between 20-29 years old, 58.7% had 8-11 years of schooling, 53.3% were white, and 73.9% lived with a partner; occurrence of hepatitis B was 0.13% (95%CI 0.04; 0.21); of the eight children of mothers with chronic hepatitis B, six had a complete vaccination schedule, and there was no vertical or perinatal transmission. Conclusion: there was low occurrence of hepatitis B in pregnant women and absence of vertical or perinatal transmission.

Adverse events following Quadrivalent HPV vaccination reported in Sao Paulo State, Brazil, in the first three years after introducing the vaccine for routine immunization (March 2014 to December 2016).

In March 2014, the Quadrivalent human papilloma virus vaccine (4vHPV) was introduced in the female adolescents vaccination schedule of the National Immunization Program (PNI). A school-based vaccination program was implemented. We conducted a retrospective, descriptive study of the adverse events that took place after HPV vaccination, reported to the Adverse Events Following Immunization (AEFI) Information System in Sao Paulo State, from March 2014 to December 2016. All reports that fit the definitions of the 2014 National Manual on AEFI surveillance were included. AEFI risk was estimated by dividing the number of reports by the number of vaccine doses administered in the period. In the three-year period, 3,390,376 HPV vaccine doses were administered and 465 AEFI reports were registered, with 1,378 signs and symptoms. The reporting rate was 13.72 per 100,000 vaccine doses administered. The reports peaked in the first year of the program. The most frequent AEFI was syncope, with 5.7 reports per 100,000 doses administered, followed by dizziness, malaise, headache and nausea. Overall, 39 AEFI cases (8.4%) were classified as severe , with a reporting rate of 1.15 per 100,000 vaccine doses administered. Most cases were classified as severe because of hospitalization. Among them, there were cases of Guillain-Barré Syndrome, deep vein thrombosis, seizures and miscarriage. All young women recovered without sequelae. We identified five clusters of AEFI reports in four cities; the larger AEFI cluster occurred in the city of Bertioga, in September 2014, involving 13 female adolescents. Our data are in accordance with those from other countries and corroborate the safety of HPV vaccines.

Association between the timing of maternal vaccination and newborns' anti-pertussis toxin antibody levels.

BACKGROUND: Pertussis remains an important global public health concern, despite the presence of extensive immunization programs. Incidence and severity of pertussis are typically higher in neonates and young infants. As a strategy to protect these young infants, maternal vaccination with Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) has been recommended in Brazil. The objective of this study was to evaluate the effects of Tdap vaccination during pregnancy on the anti-pertussis toxin (PT) IgG response in mothers and their infants at birth. MATERIAL AND METHODS: Maternal and cord blood samples were collected from vaccinated (n = 243) and unvaccinated (n = 75) pregnant women, at the time of delivery, from July 2015 to August 2016 in São Paulo, Brazil. Anti-PT IgG antibodies were quantified by Enzyme-Linked Immunosorbent Assay (ELISA) and geometric mean concentrations (GMC) were calculated. Relationship between timing of vaccination and antibody concentrations were evaluated. RESULTS: Maternal and cord blood GMCs among the vaccinated group were 5.4 and 5.6 fold higher [66.5 International Units (IU)/mL and 89.8 IU/mL] compared to the unvaccinated group (12.4 IU/mL and 16.1 IU/mL), respectively (p < 0.001). Higher anti-PT IgG GMCs were observed when vaccination occurred ≥60 days before delivery compared to <60 days, suggesting that vaccination early in the third trimester may be more effective than later in pregnancy. CONCLUSION: Tdap maternal vaccination results in significantly higher anti-PT IgG in newborn infants and supports the current recommendation of the Brazilian Immunization Program.

The effectiveness of maternal pertussis vaccination in protecting newborn infants in Brazil: A case-control study.

INTRODUCTION: In 2014, the Brazilian Ministry of Health (MoH) recommended Tdap to pregnant women in response to a significant increase in the incidence of pertussis among infants. The present study assessed the effectiveness of maternal immunization in preventing pertussis in infants. METHODS: An unmatched case-control study was undertaken in São Paulo State, Brazil from February 2015 to July 2016. Cases were infants aged <8 weeks at onset of pertussis reported to the Surveillance System and confirmed by real-time polymerase chain reaction or culture. Four to six healthy infants were selected as controls per case from birth certificates in the Information System on Live Births database. General characteristics and mother's vaccination status were compared between cases and controls. The vaccine effectiveness (VE) was calculated as 1 - odds ratio (OR). For the adjusted VE, the OR was calculated using logistic regression analysis. RESULTS: Forty-two cases and 248 controls were enrolled in the study. Mothers of 8 cases (19.1%) and 143 controls (57.4%) were vaccinated during pregnancy, resulting in an unadjusted VE of 82.6% (95% confidence interval [CI], 60.8-92.3%). The VE was unchanged after adjusting for maternal age and monthly household income. CONCLUSION: Maternal pertussis vaccination during pregnancy was effective in protecting infants aged <8 weeks from pertussis.

The role of pregnant women with rash in the Zika virus sentinel surveillance.

INTRODUCTION: The state of São Paulo has been monitoring cases of microcephaly and pregnant women presenting with acute rash, through CeVeSP. METHODS: This was a descriptive study focusing on pregnant women with rash and the outcome of their pregnancy, based on the notifications through the CeVeSP. RESULTS: During 2016, 2,209 cases of pregnant women with rash were reported and investigated. Of these, 36.6% were confirmed. Of the pregnant women who tested positive for ZIKV, 6.4% did not have a favorable outcome. CONCLUSIONS: Our results allowed the characterization of pregnant women exposed to ZIKV and the outcome of pregnancy.

The role of pregnant women with rash in the Zika virus sentinel surveillance

INTRODUCTION: The state of São Paulo has been monitoring cases of microcephaly and pregnant women presenting with acute rash, through CeVeSP. METHODS: This was a descriptive study focusing on pregnant women with rash and the outcome of their pregnancy, based on the notifications through the CeVeSP. RESULTS: During 2016, 2,209 cases of pregnant women with rash were reported and investigated. Of these, 36.6% were confirmed. Of the pregnant women who tested positive for ZIKV, 6.4% did not have a favorable outcome. CONCLUSIONS Our results allowed the characterization of pregnant women exposed to ZIKV and the outcome of pregnancy.

The role of pregnant women with rash in the Zika virus sentinel surveillance

Abstract INTRODUCTION: The state of São Paulo has been monitoring cases of microcephaly and pregnant women presenting with acute rash, through CeVeSP. METHODS: This was a descriptive study focusing on pregnant women with rash and the outcome of their pregnancy, based on the notifications through the CeVeSP. RESULTS: During 2016, 2,209 cases of pregnant women with rash were reported and investigated. Of these, 36.6% were confirmed. Of the pregnant women who tested positive for ZIKV, 6.4% did not have a favorable outcome. CONCLUSIONS Our results allowed the characterization of pregnant women exposed to ZIKV and the outcome of pregnancy.

Descriptive report of cases of congenital syndrome associated with Zika virus infection in the state of São Paulo, Brazil, from 2015 to 2017. / Descrição dos casos de síndrome congênita associada à infecção pelo ZIKV no estado de São Paulo, no período 2015 a 2017.

OBJECTIVE: to characterize cases of congenital syndrome associated with Zika virus infection (CZS) and other infectious etiologies, resident in the state of São Paulo, Brazil, from October 30, 2015, to June 30, 2017. METHODS: this was a descriptive study of suspected cases of CZS and other infectious etiologies notified on the Public Health Events Registry. RESULTS: 960 cases were investigated up to epidemiological week 26/2017, and 146 were confirmed for congenital infection; of these, 59 (40.4%) were confirmed for congenital infection without etiological identification and 87 (59.6%) with laboratory confirmation, of which 55 were congenital syndrome associated with Zika virus and 32 were congenital syndrome associated with other infectious agents. CONCLUSION: this study enabled the detection of 23.9% CZS cases among suspected cases of infectious etiology.