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. measles (MMR 2 . (HSCT) 1 postHSCT post nonimmunosuppressed non immunosuppressed ProgramMinistry Program Ministry Health 2006 city Brazil 201 2021 8 756 75 6 75.6 90.1% 901 90 (90.1 451 45 45.1 posttransplantation. posttransplantation transplantation. transplantation post-transplantation (HSCT 200 20 202 7 75. 90.1 9 (90. 4 45. 90. (90 (9 (

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). H3N2 HN H N (H3N2 5 H1N1 (JSLE literature shortterm short term ASingapore Singapore (HC INFIMH160019/2016H3N2like INFIMH1600192016H3N2like INFIMHHNlike INFIMH 16 0019/2016 like 0019 2016 SP, (SP) SC, (SC) GMT, (GMT) FIGMT FI (FI-GMT postvaccination. postvaccination post vaccination. vaccination post-vaccination activity (AE evaluated 14.5 145 [14. 10.1–18.3 101183 10 1 18 3 (10.1–18.3 vs 9–18.4 9184 (9–18.4 0.448 0448 0 448 21 87.5% 875 87 (87.5% 65.5%, 655 65.5% 65 (65.5%) 0.108. 0108 0.108 . 108 0.108] 22 91.7% 917 91 7 (91.7% 86.2%, 862 86.2% 86 (86.2%) 0.678 0678 678 102.3 1023 102 [102. 95% 95 (95 75.0–139.4 7501394 75 139 1096 109 6 109. 68.2–176.2, 6821762 68.2–176.2 68 176 68.2–176.2) 0.231. 0231 0.231 231 0.231] D30 D 100% 100 (100% 96.6%, 966 96.6% 96 (96.6%) 1.000, 1000 1.000 000 1.000)] [ 16.7% 167 (16.7% 31.0%, 310 31.0% 31 (31.0%) 0.338, 0338 0.338 338 0.338) 162.3 1623 162 [162. 132.9–198.3 13291983 132 198 (132.9–198.3 2081 208 208. 150.5–287.8, 15052878 150.5–287.8 150 287 8 (150.5–287.8) 0.143 0143 143 1.6 [1. 1.2–2.1 1221 (1.2–2.1 1. 1.4–2.5, 1425 1.4–2.5 (1.4–2.5) 0.574. 0574 0.574 574 0.574] SLEDAI2K SLEDAIK 2K K 0–17 017 17 (0–17 0–17, 0.765 0765 765 0.713, 0713 0.713 713 0.713) 0.420, 0420 0.420 420 0.420) 1.0, 1.0 1.0) 0.185, 0185 0.185 185 0.185) 0.095. 0095 0.095 095 0.095) 58.3% 583 58 (58.3 44 44.8% 0.958. 0958 0.958 958 0.958) 0.05. 005 0.05 05 0.05) H3N2influenza HNinfluenza vaccineinduced induced wwwclinicaltrialsgov www clinicaltrials gov NCT03540823. NCT03540823 NCT NCT03540823) H3N (H3N H1N INFIMH160019 2016H3N2like 00192016 0019/201 001 201 (SP (SC (GMT 14. [14 10.1–18. 10118 (10.1–18. 9–18. 918 (9–18. 0.44 044 87.5 (87.5 65.5 (65.5% 010 0.10 91.7 (91.7 86.2 (86.2% 0.67 067 67 102. [102 (9 75.0–139. 750139 13 682176 68.2–176. 023 0.23 23 D3 (100 96.6 (96.6% 1.00 00 1.000) 16.7 (16.7 31.0 (31.0% 033 0.33 33 162. [162 132.9–198. 1329198 (132.9–198. 20 1505287 150.5–287. 15 (150.5–287.8 0.14 014 [1 1.2–2. 122 (1.2–2. 142 1.4–2. (1.4–2.5 057 0.57 57 0–1 01 (0–1 0.76 076 76 071 0.71 71 042 0.42 42 018 0.18 009 0.09 09 58.3 (58. 44.8 0.95 0.0 NCT0354082 INFIMH16001 HNlike 0019201 0019/20 10.1–18 1011 (10.1–18 9–18 (9–18 0.4 04 87. (87. 65. (65.5 0.1 91. (91. 86. (86.2 0.6 06 [10 75.0–139 75013 68217 68.2–176 02 0.2 (10 96. (96.6 16. (16. 31. (31.0 03 0.3 [16 132.9–198 132919 (132.9–198 150528 150.5–287 (150.5–287. 1.2–2 12 (1.2–2 1.4–2 (1.4–2. 0.5 0– (0– 0.7 07 58. (58 44. 0.9 0. NCT035408 INFIMH1600 001920 0019/2 10.1–1 101 (10.1–1 9–1 (9–1 (87 (65. (91 (86. 75.0–13 7501 6821 68.2–17 (1 (96. (16 (31. 132.9–19 13291 (132.9–19 15052 150.5–28 (150.5–287 1.2– (1.2– 1.4– (1.4–2 (0 (5 NCT03540 INFIMH160 00192 0019/ 10.1– (10.1– 9– (9– (8 (65 (86 75.0–1 750 682 68.2–1 (96 (31 132.9–1 1329 (132.9–1 1505 150.5–2 (150.5–28 1.2 (1.2 1.4 (1.4– NCT0354 INFIMH16 10.1 (10.1 (6 75.0– 68.2– (3 132.9– (132.9– 150.5– (150.5–2 (1. (1.4 NCT035 INFIMH1 10. (10. 75.0 68.2 132.9 (132.9 150.5 (150.5– NCT03 75. 68. 132. (132. 150. (150.5 NCT0 (132 (150. (13 (150 (15

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.

ABSTRACT This observational retrospective study conducted during an yellow fever (YF) outbreak in Sao Paulo, Brazil, in 2017-2018, describes adverse events (AE) following YF vaccination of immunocompromised persons. Risks and benefits of vaccination were individually evaluated by physicians. AE were assessed by phone call or electronic mail, 14 to 90 days after vaccination. Three hundred and eighty one immunocompromised persons received a full-dose of YF vaccine. Their age ranged from 1.4 to 89.3 years (median 50.8 years); 53% were women; 178 (46.7%) had chronic kidney disease, 78 (20.5%) had immune-mediated inflammatory diseases; 94 (24.7%) were using or had recently used immunosuppressive/ immunomodulatory drugs. All of them denied previous YF vaccination. We were able to contact 341 (89.5%) vaccinees: 233 (68.3%) of them received the YF vaccine from BioManguinhos and 108 (31.7%) received the vaccine from Sanofi-Pasteur; 130 (38.1%) vaccinees received other vaccines (up to 4) simultaneously with the the YF vaccine, mostly hepatitis B (59 vaccinees), pneumococcal polysaccharide 23-valent (46), influenza (43) and diphtheria-tetanus (dT, 41). One hundred and eleven vaccinees (32.6%) reported at least one AE: 79 (23.2%) presented systemic AE, 44 (12.9%) had local AE and 12 had both, local and systemic AE. The most common AE was pain at the injection site (41 persons, 12%), myalgia (34; 10%), fever (25; 7.3%) and headache (16; 4.7%). There was no statistically significant difference on the AE frequency according to the vaccine producer. There were four severe AE: one hospitalization and three deaths, considered not related to the YF vaccine.

ABSTRACT Candidemia is a significant cause of bloodstream infections (BSI) in nosocomial settings. The identification of species can potentially improve the quality of care and decrease human mortality. Quantitative PCR (qPCR) was evaluated for Candida albicans detection using culture suspensions containing C. albicans , spiked human blood, the cloned qPCR target fragment (ITS2 region) and the results of these assays were compared. The assays showed a good detection limit: C. albicans DNA extracted from yeast (sensitivity 0.2 CFU/µL), spiked human blood (sensitivity 10 CFU/mL), and cloned fragment of ITS2 region (sensitivity 20 target copies/μL). The efficiency of ITS2 fragment-qPCR ranged from 89.67 to 97.07, and the linearity (R2) of the standard curve ranged from 0.992 to 0.999. The results showed that this ITS2-qPCR has a great potential as a molecular prototype model for the development of a test to be applied in clinical practice, greatly reducing the time of candidemia diagnosis, which is extremely important in this clinical setting.

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.

ABSTRACT Trypanosoma cruzi is the causative agent of Chagas disease. Nowadays, the transmission in Brazil occurs mainly by oral ingestion of contaminated food that has been associated with more severe clinical manifestations. We report a case of Acute Chagas disease caused by oral transmission in a child from Northern Brazil. In the hospital admission, physical examination showed tachycardia, hepatomegaly, bipalpebral edema and anasarca. Trypanosoma cruzi trypomastigotes were found in microscopy during blood cell count. Twenty-three days before hospitalization, the child had ingested the “bacaba palm fruit's wine”. Even with the appropriate diagnosis and starting of treatment, she did not survive. Quantitative analysis of Trypanosoma cruzi DNA in a blood sample resulted in 54,053.42 parasite equivalents/mL and the DTU TcIV was identified. The outcome may have been determined by several factors, including the delay to seek a medical service beyond the high parasitemia, detected by qPCR. DTU TcIV could also have influenced the natural history of the disease.

ABSTRACT Annual vaccination is the most effective way to prevent seasonal influenza illness. Instituto Butantan (IB) performed clinical studies with its 2013, 2014 and 2015 seasonal trivalent influenza vaccines (inactivated split-virion). Prospective cohort studies were carried out to describe the safety and immunogenicity of Instituto Butantan influenza vaccines, in healthy adults and elderly, from 2013 to 2015. Immediately after the informed consent was signed, participants underwent blood collection followed by vaccination. On study days 1, 2 and 3 post-vaccination participants were contacted by the staff to evaluate the occurrence of solicited (local and systemic) and non-solicited adverse reactions. On study day 21 (+7) subjects returned to the clinical site for final safety assessments and blood collection to evaluate post-vaccination immunogenicity. The immunogenicity analyses were performed by means of hemagglutination inhibition (HI) assay. The immunogenicity endpoints were: seroprotection (SPR) and seroconversion (SCR) rates and the geometric mean HI antibody titer ratio (GMTR). The 2013 study was conducted at the Centro de Referência para Imunobiológicos Especiais (CRIE) and at the Centro de Pesquisa Clínica do Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo while the 2014 and 2015 studies were conducted at CRIE. The vaccine composition followed the WHO recommendation for the Southern hemisphere seasonal influenza vaccine. Forty-seven healthy adults and 13 elderly participated in the 2013 study, 60 healthy adults and 60 elderly in the 2014 study, and 62 healthy adults and 57 elderly in the 2015 study. In the 2013, 2014 and 2015 studies, pain was the most frequent local adverse reaction and headache the most frequent systemic adverse reaction. All observed adverse reactions were classified as mild or moderate and none as severe. SPR >70% and SPR >60% were observed in adults and elderly, respectively, for the three vaccine viruses, in the 2013, 2014 and 2015 studies. SCR >40% was observed in adults, for the three vaccine viruses, only in the 2014 study and SCR >30% was observed in the elderly, for the three vaccine viruses, only in the 2013 and 2014 studies. GMTR >2.5 among adults, for the three vaccine viruses was only observed in the 2013 study and GMTR >2.0 was observed among elderly, for the three vaccine viruses, in the 2013, 2014 and 2015 studies. The 2013, 2014 and 2015 seasonal influenza vaccines produced by Instituto Butantan were safe and immunogenic according to the immunogenicity criteria defined by the European Medicines Agency (EMA).

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.

SUMMARY Neisseria meningitidis is a cause of several life-threatening diseases and can be a normal commensal in the upper respiratory tract of healthy carriers. The carrier rate is not well established especially because there is no standard method for the isolation of N. meningitidis. Therefore, the aim of this study was to compare identification methods for the carrier state. Two swabs were collected from 190 volunteers: one was cultured and the other had DNA extracted directly from the sample. The Polymerase Chain Reaction (PCR) was performed to determine species and serogroups and compared the results between the methods. PCR for species determination used two pairs of primers and when there was only one amplicon, it was sequenced. The culture technique was positive in 23 (12.1%) subjects while the direct extraction method was positive in 132 (69.5%), p < 0.001. Among the 135 subjects with positive N. meningitides tests, 88 (65.2%) were serogroup C; 3 (2.2%) serogroup B; 5 (3.7%) were positive for both serogroup B and C, and 39 (28.9%) did not belong to any of the tested serogroups. In this study, PCR from DNA extracted directly from swabs identified more N. meningitidis asymptomatic carriers than the culture technique.

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.

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.

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.

INTRODUÇÃO: Esse estudo avaliou a resposta à revacinação contra hepatite B (HB) entre profissionais de saúde (PS) com anti-HBs negativo após esquema de vacinação completo. MÉTODOS: PS cujo anti-HBs foi realizado > 90 dias após a última dose do esquema vacinal receberam 4ª dose da vacina. O anti-HBs foi repetido 30-90 dias após. RESULTADOS: Entre 170 PS, 126 (74,1%) tiveram anti-HBs positivo após a 4ª dose. CONCLUSÕES: Repetir o teste sorológico após a 4ª dose é estratégia prática caso o anti-HBs tenha sido realizado > 90 dias após a última dose da vacina.

INTRODUCTION: This study aimed to evaluate the response to hepatitis B (HB) revaccination of healthcare workers (HCW) who are negative for antibodies to HB surface antigen (anti-HBs) after a complete vaccination series. METHODS: HCW whose anti-HBs test was performed > 90 days after a HB vaccination course were given a 4th dose. A post-vaccination test was done within 30 to 90 days. RESULTS: One hundred and seventy HCW were enrolled: 126 (74.1%) were anti-HBs-positive after the 4th dose. CONCLUSIONS: Rechecking anti-HBs after the 4th HB vaccine dose is a practical approach in case of post-vaccination tests performed >90 days after the full vaccination course.