The decline of measles antibody titers in previously vaccinated adults: a cross-sectional analysis

ABSTRACT The global reemergence of measles in 2018-2019 reinforces the relevance of high-coverage immunization to maintain the disease elimination. During an outbreak in the Sao Paulo State in 2019, several measles cases were reported in individuals who were adequately vaccinated according to the current immunization schedule recommends. This study aimed to assess measles IgG antibody seropositivity and titers in previously vaccinated adults. A cross-sectional study was conducted at CRIE-HC-FMUSP (Sao Paulo, Brazil) in 2019. It included healthy adults who had received two or more Measles-Mumps-Rubella vaccines (MMR) and excluded individuals with immunocompromising conditions. Measles IgG antibodies were measured and compared by ELISA (Euroimmun®) and chemiluminescence (LIASON®). The association of seropositivity and titers with variables of interest (age, sex, profession, previous measles, number of measles-containing vaccine doses, interval between MMR doses, and time elapsed since the last MMR dose) was analyzed. A total of 162 participants were evaluated, predominantly young (median age 30 years), women (69.8%) and healthcare professionals (61.7%). The median interval between MMR doses was 13.2 years, and the median time since the last dose was 10.4 years. The seropositivity rate was 32.7% by ELISA and 75.3% by CLIA, and a strong positive correlation was found between the tests. Multivariate analyses revealed that age and time since the last dose were independently associated with positivity. Despite being a single-center evaluation, our results suggest that measles seropositivity may be lower than expected in adequately immunized adults. Seropositivity was higher among older individuals and those with a shorter time since the last MMR vaccine dose.

Detection of Trypanosoma cruzi DTUs TcI and TcIV in two outbreaks of orally-transmitted Chagas disease in the Northern region of Brazil

ABSTRACT This study describes the laboratory investigation of two acute Chagas disease outbreaks that occurred in the riverside communities of Marimarituba and Cachoeira do Arua, in the Santarem municipality, Para State, located in the Northern region of Brazil, and occurred in March 2016 and August 2017, respectively. The generation of data regarding the diversity of Trypanosoma cruzi parasites circulating in the Amazon region is key for understanding the emergence and expansion of Chagas disease. This study aimed to identify T. cruzi Discrete Typing Units (DTUs) involved in two outbreaks of acute Chagas disease (ACD) directly from the patient's biological sample. Nested and multiplex PCR targeting the 24Sα (rRNA) and mini-exon genes, respectively, were used to identify T. cruzi DTU in blood samples from patients diagnosed with ACD. The samples with positive cPCR were submitted for analysis for T. cruzi DTUs, which included 13 samples from the patients with ACD by oral transmission and two samples collected from two newborns of two women with ACD, from Marimarituba and Cachoeira do Arua. The samples were classified as T. cruzi TcIV, from Marimarituba's outbreak, and T. cruzi TcI, from Cachoeira do Arua's outbreak. The molecular identification of T. cruzi may increase understanding of the role of this parasite in Chagas disease's emergence within the Amazon region, contributing to the improvement of the management of this important, but also neglected, disease.

Measles, mumps and rubella vaccine 12 months after hematopoietic stem cell transplantation

ABSTRACT The measles, mumps and rubella (MMR) vaccine is usually recommended from 24 months after a hematopoietic stem cell transplant (HSCT). Some authors have demonstrated that the MMR vaccination can be safe from 12 months post-HSCT in non-immunosuppressed patients, as recommended by the Brazilian National Immunization Program/Ministry of Health, since 2006. The objectives of this study were to evaluate when patients received MMR vaccine after an HSCT in our care service and if there were reports of any side effects. We retrospectively reviewed the records of HSCT recipients who received at least one MMR dose in our care service, a quaternary teaching hospital in Sao Paulo city, Brazil, from 2017 to 2021. We identified 82 patients: 75.6% (90.1% in the autologous group and 45.1% in the allogeneic group) were vaccinated before 23 months post-transplantation. None reported side effects following the vaccination. Our data support that the MMR vaccination is safe from 12 to 23 months after HSCT.

Safety and immunogenicity of influenza A(H3N2) component vaccine in juvenile systemic lupus erythematosus

Abstract Introduction Seasonal influenza A (H3N2) virus is an important cause of morbidity and mortality in the last 50 years in population that is greater than the impact of H1N1. Data assessing immunogenicity and safety of this virus component in juvenile systemic lupus erythematosus (JSLE) is lacking in the literature. Objective To evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in JSLE. Methods 24 consecutive JSLE patients and 29 healthy controls (HC) were vaccinated with influenza A/Singapore/ INFIMH-16-0019/2016(H3N2)-like virus. Influenza A (H3N2) seroprotection (SP), seroconversion (SC), geometric mean titers (GMT), factor increase in GMT (FI-GMT) titers were assessed before and 4 weeks post-vaccination. Disease activity, therapies and adverse events (AE) were also evaluated. Results JSLE patients and controls were comparable in current age [14.5 (10.1-18.3) vs. 14 (9-18.4) years, p = 0.448] and female sex [21 (87.5%) vs. 19 (65.5%), p = 0.108]. Before vaccination, JSLE and HC had comparable SP rates [22 (91.7%) vs. 25 (86.2%), p = 0.678] and GMT titers [102.3 (95% CI 75.0-139.4) vs. 109.6 (95% CI 68.2-176.2), p = 0.231]. At D30, JSLE and HC had similar immune response, since no differences were observed in SP [24 (100%) vs. 28 (96.6%), p = 1.000)], SC [4 (16.7%) vs. 9 (31.0%), p = 0.338), GMT [162.3 (132.9-198.3) vs. 208.1 (150.5-287.8), p = 0.143] and factor increase in GMT [1.6 (1.2-2.1) vs. 1.9 (1.4-2.5), p = 0.574]. SLEDAI-2K scores [2 (0-17) vs. 2 (0-17), p = 0.765] and therapies remained stable throughout the study. Further analysis of possible factors influencing vaccine immune response among JSLE patients demonstrated similar GMT between patients with SLEDAI < 4 compared to SLEDAI ≥ 4 ( p = 0.713), as well as between patients with and without current use of prednisone ( p = 0.420), azathioprine ( p = 1.0), mycophenolate mofetil ( p = 0.185), and methotrexate ( p = 0.095). No serious AE were reported in both groups and most of them were asymptomatic (58.3% vs. 44.8%, p = 0.958). Local and systemic AE were alike in both groups ( p > 0.05). Conclusion This is the first study that identified adequate immune protection against H3N2-influenza strain with additional vaccine-induced increment of immune response and an adequate safety profile in JSLE. ( www.clinicaltrials.gov , NCT03540823).

Adverse events following immunization of elderly with COVID-19 inactivated virus vaccine (CoronaVac) in Southeastern Brazil: an active surveillance study

ABSTRACT Healthcare workers, the elderly and other vulnerable populations were the first to receive COVID-19 vaccines in public health programs. There were few vaccine safety data available on the elderly. This observational study aimed to evaluate the inactivated vaccine (CoronaVac) safety in the elderly, at the beginning of the vaccination program, in Sao Paulo city, Brazil. The elderly people that received CoronaVac at the Reference Center for Special Immunobiologicals (CRIE) or at home, administered by the Interdisciplinary Home Care Team (NADI) of the Hospital das Clinicas were invited to participate in this phase 4 observational study. The vaccination schedule included two CoronaVac doses 28 days apart. The information on solicited and unsolicited adverse events following immunization were collected by phone calls on days 4 and 8 after each vaccine dose. We enrolled 158 adults aged 65 to 101 years (mean of 84.1 years); 63.9% were females and 95.6% had chronic conditions, 21.5% had moderate or severe impairment in daily living activities; 34.2% were pre-frail and 19.6% were frail. We were able to contact 95.6% and 91.6% of the vaccinated people, after the first and second doses, respectively; 31.8% and 23.4% of the contacted participants reported some adverse events (AE) following the first and second doses, respectively. Pain at the injection site, fatigue, myalgia and headaches were the most frequent solicited AE. Most AE were mild to moderate. There were eight severe adverse events, but none of them were considered related to the vaccine. The CoronaVac was safe and well tolerated by these adults of advanced age with frailty and comorbidities.

Low tetanus-diphtheria-acellular pertussis (Tdap) vaccine coverage among healthcare workers in a quaternary university hospital in São Paulo, Brazil: need for continuous surveillance and implementation of active strategies

Abstract Introduction: Vaccination with tetanus-diphtheria-acellular pertussis (Tdap) has been recommended for healthcare workers (HCWs) by Brazilian Ministry of Health since November 2014. Objective: To describe the strategies implemented to improve Tdap uptake, cumulative vaccine coverage after each intervention, variables associated to Tdap vaccination, and reasons for non-vaccination among HCWs of the main building of a quaternary hospital attached to the Sao Paulo University Medical School. Methods: A list of HCWs eligible for pertussis vaccination was generated. From April to December 2015, the following interventions were implemented: note on intern journal reminding the importance of pertussis vaccination; email to the head nurses strengthening vaccine recommendations; lectures on pertussis and Tdap for physicians of Obstetrics and Neonatology Clinics; on-site vaccination by mobile teams at the Obstetrics, Neonatology, and Anesthesiology Clinics. Vaccine coverage was accessed at the end of each month. Multivariate Poisson regression model with a robust error variance was used to evaluate variables associated with Tdap vaccination. Reasons for non-vaccination were evaluated from January to May 2017 through phone calls for HCWs who had not received Tdap. Results: The study included 456 HCWs. After the interventions, Tdap coverage raised from 2.8% to 41.2%. In the multivariate analysis, occupation (physician), working place (obstetrics or anesthesiology) and influenza vaccination in 2015 were independently associated to Tdap vaccination. The main reason for non-vaccination was unawareness of Tdap recommendations. Conclusions: Tdap uptake among HCWs was low in our hospital. Providing vaccination at convenient places/times for HCW seems to be the most efficient strategy to increase vaccine uptake.

A Brazilian university hospital position regarding transplantation criteria for HIV-positive patients according to the current literature

Human immunodeficiency virus (HIV) infection was considered a contraindication for solid organ transplantation (SOT) in the past. However, HIV management has improved since highly active antiretroviral therapy (HAART) became available in 1996, and the long-term survival of patients living with HIV has led many transplant programs to reevaluate their policies regarding the exclusion of patients with HIV infection. Based on the available data in the medical literature and the cumulative experience of transplantation in HIV-positive patients at our hospital, the aim of the present article is to outline the criteria for transplantation in HIV-positive patients as recommended by the Immunocompromised Host Committee of the Hospital das Clínicas of the University of São Paulo.

Prevalence and titers of yellow fever virus neutralizing antibodies in previously vaccinated adults

ABSTRACT Introduction: The World Health Organization (WHO) recommends one single dose of the Yellow Fever (YF) vaccine based on studies of antibody persistency in healthy adults. We assessed the prevalence and titers of YF virus neutralizing antibodies in previously vaccinated persons aged ≥ 60 years, in comparison to younger adults. We also evaluated the correlation between antibody titers and the time since vaccination among participants who received one vaccine dose, and the seropositivity among participants vaccinated prior to or within the past 10 years. Methods: previously vaccinated healthy persons aged ≥ 18 years were included. YF virus neutralizing antibody titers were determined by means of the 50% Plaque Reduction Neutralization Test. Results: 46 persons aged ≥ 60 years and 48 persons aged 18 to 59 years were enrolled. There was no significant difference in the prevalence of YF virus neutralizing antibodies between the two groups (p = 0.263). However, titers were significantly lower in the elderly (p = 0.022). There was no correlation between YF virus neutralizing antibody titers and the time since vaccination. There was no significant difference in seropositivity among participants vaccinated prior to or within the past 10 years. Conclusions: the clinical relevance of the observed difference in YF virus neutralizing antibody titers between the two groups is not clear.

Avaliação da rede de frio para conservação de vacinas em unidades básicas de saúde das regiões Sul e Centro-Oeste do município de São Paulo em 2011-2012 / Evaluation of the cold chain for vaccine conservation in primary healthcare centers in the South and Midwest regions of São Paulo city, Brazil, in 2011-2012 / Evaluación de la cadena de frío para la conservación de vacunas en Unidades Básicas de Salud de las regiones Sur y Medio-Oeste de São Paulo en 2011-2012

OBJETIVO: avaliar capacidade da rede de frio (RF), conhecimento dos profissionais e práticas de conservação de imunobiológicos em unidades básicas de saúde (UBS) do município de São Paulo. MÉTODOS: estudo descritivo envolvendo amostra randômica de 24 UBS das regiões Sul e Centro-Oeste do município; de dezembro de 2011 a julho de 2012, foram entrevistados profissionais quanto ao conhecimento/prática em conservação de vacinas e observou-se a infraestrutura local, utilizando-se formulário desenvolvido para o projeto, sobre cujos itens atribuíram-se pontos e classificou-se cada UBS - suficiente, regular e insuficiente. RESULTADOS: a maioria das 24 UBS avaliadas era administrada por organizações sociais; todas possuíam câmaras de vacinas, cinco referiram utilizar sua capacidade máxima de armazenamento, nove UBS foram classificadas como de conhecimento/prática suficiente e 15 como de conhecimento/prática regular. CONCLUSÃO: a utilização da RF nessas UBS estava próxima da capacidade máxima; muitos profissionais não tinham conhecimentos básicos sobre conservação de vacinas.

OBJECTIVE: to assess the cold chain capacity, health workers' immunobiological product conservation knowledge and practices in Primary Healthcare Centers (PHC) in São Paulo city, Brazil. METHODS: this descriptive study included 24 randomly selected PHC in the South and Midwest regions of the city; between December 2011 and July 2012, we interviewed the health workers on their vaccine conservation knowledge/practice and observed the local infrastructure, using a form developed for this project; we assigned points to items of the form and classified each PHC as sufficient, regular or insufficient. RESULTS: most of the 24 PHC evaluated were administered by Social Organizations; all of them had vaccine storage chambers; 5 PHC reported using their maximum storage capacity; 9 PHC were classified as having sufficient knowledge/practice and 15 as having regular knowledge/practice. CONCLUSION: in these PHC, cold chain utilization was close to its maximum capacity; many health workers did not have basic knowledge about vaccine conservation.

OBJETIVO: evaluar la cadena de frío (CF), el conocimiento de los profesionales y las prácticas de conservación de vacunas en unidades básicas de salud (UBS) de São Paulo-SP, Brasil. MÉTODOS: estudio descriptivo de una muestra aleatoria de 24 UBS en las regiones Sur y Centro-Oeste del municipio; de diciembre del 2011 a julio del 2012, fueron entrevistados profesionales con respecto a sus conocimientos y prácticas en la conservación de vacunas, concomitantementese observó la infraestructura, utilizando un formulario desarrollado para el proyecto; atribuyéndose un puntaje específico para cada ítem, clasificamos las UBS como suficientes, regulares o insuficientes. RESULTADOS: la mayoría de las 24 UBS eran administradas por organizaciones sociales; todos tenían cámaras de vacunas; cinco informaron usar su capacidad máxima de almacenamiento; 9 UBS fueron clasificadas como suficientes y 15 como regulares. CONCLUSIÓN: la utilización de la CF en estas UBS estaba próxima al máximo; muchos profesionales no tenían conocimientos básicos acerca de conservación de vacunas.

Cytomegalovirus infection in transplant recipients

Cytomegalovirus infection is a frequent complication after transplantation. This infection occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative patients and can be defined as follows: latent infection, active infection, viral syndrome or invasive disease. This condition occurs mainly between 30 and 90 days after transplantation. In hematopoietic stem cell transplantation in particular, infection usually occurs within the first 30 days after transplantation and in the presence of graft-versus-host disease. The major risk factors are when the recipient is cytomegalovirus seronegative and the donor is seropositive as well as when lymphocyte-depleting antibodies are used. There are two methods for the diagnosis of cytomegalovirus infection: the pp65 antigenemia assay and polymerase chain reaction. Serology has no value for the diagnosis of active disease, whereas histology of the affected tissue and bronchoalveolar lavage analysis are useful in the diagnosis of invasive disease. Cytomegalovirus disease can be prevented by prophylaxis (the administration of antiviral drugs to all or to a subgroup of patients who are at higher risk of viral replication) or by preemptive therapy (the early diagnosis of viral replication before development of the disease and prescription of antiviral treatment to prevent the appearance of clinical disease). The drug used is intravenous or oral ganciclovir; oral valganciclovir; or, less frequently, valacyclovir. Prophylaxis should continue for 90 to 180 days. Treatment is always indicated in cytomegalovirus disease, and the gold-standard drug is intravenous ganciclovir. Treatment should be given for 2 to 3 weeks and should be continued for an additional 7 days after the first negative result for viremia. .

Management of post-transplant Epstein-Barr virus-related lymphoproliferative disease in solid organ and hematopoietic stem cell recipients

Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) is one of the most serious complications associated with solid organ and hematopoietic stem cell transplantation. PTLD is most frequently seen with primary EBV infection post-transplant, a common scenario for pediatric solid organ recipients. Risk factors for infection or reactivation of EBV following solid organ transplant are stronger immunosuppressive therapy regimens, and being seronegative for receptor. For hematopoietic stem cell transplantation, the risk factors relate to the type of transplant, human leukocyte antigen disparity, the use of stronger immunosuppressants, T-cell depletion, and severe graft-versus-host disease. Mortality is high, and most frequent in patients who develop PTLD in the first six months post-transplant. The primary goal of this article is to provide an overview of the clinical manifestations, diagnosis, accepted therapies, and management of EBV infection in transplant recipients, and to suggest that the adoption of monitoring protocols could contribute to a reduction in related complications.

Spontaneous reporting of adverse events following pandemic influenza A (H1N1) immunization in a reference center in the State of Sao Paulo, Brazil

Introduction This paper describes adverse events (AEs) temporally associated to the pandemic influenza A (H1N1) vaccine observed in a reference center in São Paulo, Brazil, during a 2010 mass vaccination campaign. Methods A retrospective study involving persons who sought medical care for AEs following influenza vaccination. Data were retrieved from medical records, vaccine AE notification forms, and a computerized system for immunobiological registration. Results Sixty-six vaccinees sought medical care for AEs after immunization. The most frequent AEs were fever, headache, myalgia, and pain at the injection site. No serious AEs were reported. Conclusions Few vaccinees spontaneously reported AEs to influenza A (H1N1) vaccine at this center. .

Campaign, counseling and compliance with influenza vaccine among older persons

OBJECTIVES: Population aging raises concerns regarding the increases in the rates of morbidity and mortality that result from influenza and its complications. Although vaccination is the most important tool for preventing influenza, vaccination program among high-risk groups has not reached its predetermined aims in several settings. This study aimed to evaluate the impacts of clinical and demographic factors on vaccine compliance among the elderly in a setting that includes a well-established annual national influenza vaccination campaign. METHODS: This cross-sectional study included 134 elderly patients who were regularly followed in an academic medical institution and who were evaluated for their influenza vaccination uptake within the last five years; in addition, the demographic and clinical characteristics and the reasons for compliance or noncompliance with the vaccination program were investigated. RESULTS: In total, 67.1 percent of the participants received the seasonal influenza vaccine in 2009. Within this vaccinationcompliant group, the most common reason for vaccine uptake was the annual nationwide campaign (52.2 percent; 95 percent CI: 41.4-62.9 percent); compared to the noncompliant group, a higher percentage of compliant patients had been advised by their physician to take the vaccine (58.9 percent vs. 34.1 percent; p,0.01). CONCLUSION: The education of patients and health care professionals along with the implementation of immunization campaigns should be evaluated and considered by health authorities as essential for increasing the success rate of influenza vaccination compliance among the elderly.

Vacinação dos viajantes: experiência do Ambulatório dos Viajantes do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo / Travelers' vaccinations: experience from the Travelers' Clinic of Hospital das Clínicas, University of São Paulo School of Medicine

O perfil dos indivíduos, a situação vacinal e as vacinas recomendadas aos viajantes que procuram o serviço médico de orientação pré-viagem do Ambulatório dos Viajantes do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo foram analisados no presente estudo. Dos 445 viajantes estudados, 51 por cento eram mulheres; a mediana de idade foi de 33,5 anos; 51 por cento viajavam a trabalho e 39,5 por cento por lazer. Destinos mais procurados: África (47 por cento); Ásia (31,7 por cento); América do Sul (21,4 por cento). Trezentos e oitenta e cinco (86,5 por cento) viajantes tiveram indicação de vacinação para viagem. Principais vacinas recomendadas: febre tifóide (55,7 por cento), difteria-tétano (54,1 por cento), hepatite A (46,1 por cento), hepatite B (44,2 por cento), febre amarela (24,7 por cento). A orientação pré-viagem mostrou-se importante não só para indicar as vacinas recomendadas para a viagem, mas também como oportunidade para atualização das vacinas de rotina.

TThe profile and vaccination status of travelers seeking pre-travel medical advice at the Travelers' Clinic of Hospital das Clínicas, University of São Paulo School of Medicine, and the vaccines recommended for them, were analyzed in the present study. Among the 445 travelers who were studied, 51 percent were women, the median age was 33.5 years, 51 percent were traveling on business and 39.5 percent were traveling for leisure purposes. The destinations most sought were Africa (47 percent), Asia (31.7 percent) and South America (21.4 percent). Vaccination before traveling was recommended for 385 (86.5 percent) of the travelers. The main vaccines recommended were against typhoid fever (55.7 percent), diphtheria-tetanus (54.1 percent), hepatitis A (46.1 percent), hepatitis B (44.2 percent) and yellow fever (24.7 percent). The pre-travel guidance was shown to be important not only for indicating the vaccines recommended for the trip, but also as an opportunity to update routine vaccinations.

Occurrence of early adverse events after vaccination against influenza at a brazilian reference center

INTRODUCTION: Since 1999, the Ministry of Health in Brazil has conducted campaigns of vaccination against influenza targeted towards the elderly, chronically-diseased people and health care workers. The vaccine against influenza is associated with adverse events of minor importance. OBJECTIVE: To investigate the early adverse events related to the vaccine against influenza. CASUISTICS AND METHODS: One hundred and ninety seven elderly individuals and health care workers vaccinated against influenza were included. An inquiry regarding adverse events related to the vaccine was applied seven days after the vaccination. RESULTS: Local adverse events were reported by 32.5 percent and systemic effects by 26.4 percent of the vaccinated subjects. Pain in the region of the injection, headache, myalgia, malaise, and coryza were more frequent in the workers than in the elderly (p<0.05). There was no statistically significant difference in the occurrence of fever. CONCLUSIONS: The belief of part of the population that credits frequent and uncomfortable adverse events to the vaccine was not confirmed. The subjective adverse events were more frequent in the health care workers, which can influence, in a negative way, the disclosure of the benefits of this vaccine due to their role as opinion makers.