Use of live viral vaccines after HCT: Still a lot to learn.

Revaccination program after HCT is necessary due to the loss of lifelong immunity acquired by previous vaccination or infections. The program is complex and even in a favourable scenario, it takes more than 2 years to be completed. As the complexity of HCT increases (alternative donors, diversity of monoclonal antibodies), studies evaluating the response to vaccination in this population are welcome, especially those that evaluate live attenuated vaccines given their scarcity. Furthermore, measles, mumps, rubella and even yellow fever, and poliomyelitis outbreaks have perplexed infectious diseases clinicians and epidemiologists globally, most of them due to the decline in vaccination coverage rates in children and adults, because of the growth of antivaccine movements around the world. The study of Lin et al. adds important information about measles, mumps and rubella vaccination after HCT.

Epidemiology, treatment patterns, and disease burden of cytomegalovirus in hematopoietic cell transplant recipients in selected countries outside of Europe and North America: A systematic review.

BACKGROUND: Cytomegalovirus (CMV) disease impacts morbidity and mortality in hematopoietic cell transplant (HCT) recipients. This systematic review summarized data on the epidemiology, management, and burden of CMV post-HCT outside of Europe and North America. METHODS: The MEDLINE, Embase, and Cochrane databases were searched for observational studies and treatment guidelines in HCT recipients across 15 selected countries from Asia-Pacific, Latin America, and Middle East (search period: 1 January 2011-17 September 2021). Outcomes included incidence of CMV infection/disease, recurrence, risk factors, CMV-related mortality, treatments, refractory, resistant CMV, and burden. RESULTS: Of 2708 references identified, 68 were eligible (67 studies and one guideline; 45/67 studies specific to adult allogeneic HCT recipients). The rates of CMV infection and disease within 1 year of allogeneic HCT were 24.9%-61.2% (23 studies) and 2.9%-15.7% (10 studies), respectively. Recurrence occurred in 19.8%-37.9% of cases (11 studies). Up to 10% of HCT recipients died of CMV-related causes. In all countries, first-line treatment for CMV infection/disease involved intravenous ganciclovir or valganciclovir. Conventional treatments were associated with serious adverse events such as myelosuppression (10.0%) or neutropenia only (30.0%, 39.8%) and nephrotoxicity (11.0%) (three studies), frequently leading to treatment discontinuation (up to 13.6%). Refractory CMV was reported in 2.9%, 13.0%, and 28.9% of treated patients (three studies) with resistant CMV diagnosed in 0%-10% of recipients (five studies). Patient-reported outcomes and economic data were scarce. CONCLUSION: The incidence of CMV infection and disease post-HCT is high outside of North America and Europe. CMV resistance and toxicity highlight a major unmet need with current conventional treatments.

Compliance with yellow fever and measles vaccines in the revaccination program post-hematopoietic cell transplantation.

INTRODUCTION: Measles, mumps, rubella, and even poliomyelitis outbreaks have recently perplexed infectious disease clinicians and epidemiologists globally due to the decline in vaccination coverage rates in children and adults. Measles and yellow fever (YF) have represented an increasing burden on the Brazilian public health system in recent decades. Both diseases are preventable by live-attenuated viral vaccines (LAVV), which have restricted use in hematopoietic cell transplant (HCT) recipients. METHODS: Autologous and allogeneic HCT recipients returning for regular appointments at the outpatient clinic were invited to participate in the study. Patients transplanted for at least 2 years and with a printed copy of the vaccination record were included. RESULTS: We assessed the vaccination records of 273 HCT recipients after the second year of HCT (193 allogeneic and 80 autologous) and observed lower compliance with the YF vaccine (58 patients, 21.2%) than with the measles vaccine (138 patients, 50.5%, p ≤ .0001). This is the largest published series of YF vaccination in HCT recipients so far. No severe adverse events occurred. Although expected, chronic graft-versus-host disease (GVHD) did not affect the compliance with measles (p = .08) or YF vaccination (p = .7). Indeed, more allogeneic recipients received measles vaccine in comparison with autologous patients (p < .0001), suggesting that chronic GVHD was not the main reason for not being vaccinated. Children and allogeneic HCT were more likely to receive measles vaccine. Time elapsed from HCT >5 years favored both measles and YF vaccination. CONCLUSION: A better understanding of the reasons for low compliance with LAVV is necessary to overcome this problem.

Clinical impact of multiple DNA virus infections in nondepleted haploidentical and unrelated allogeneic hematopoietic stem cell transplantation.

Few studies have compared the clinical impact of multiple DNA-virus infections in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with posttransplant cyclophosphamide (PTCy) and unrelated donor allogeneic hematopoietic stem cell transplantation (UD-HSCT) with thymoglobulin, so we retrospectively analyzed viral infections in the first 6 mo posttransplant in these scenarios. Fifty-nine patients underwent to haplo-HSCT, and 68 to UD-HSCT. The most frequent infection was cytomegalovirus (CMV) (76.3% in haplo-HSCT and 69.1% in UD-HSCT) (P = .878) and in the group of patients with CMV reactivation, maximal CMV viral load over 2500 UI/ml correlated with worse overall survival-hazard ratio (HR) 1.93 (95% confidence interval [CI] 1.04-3.59) P = .03. The cumulative incidence of multiple DNA virus within 180 d of posttransplant was 78.7% for one virus and 28.4% for two or more viruses with no difference regarding the type of transplant. Viral infections, age, and acute graft versus host disease (GVHD) grades II-IV were risk factors for worse overall survival in multivariate analyses: one virus HR 2.53 (95% CI 1.03-6.17) P = .04, two or more viruses HR 3.51 (95% CI 1.37-9) P < .01, age HR 1.03 (95% CI 1.02-1.05) P < .01 and acute GVHD II-IV HR 1.97 (95% CI 1.13-3.43) P = .01. Also, age over 50 y HR 4.25 (95% CI 2.01-8.97) P < .001, second CMV reactivation or having both CMV and BK polyomavirus (BKV) HR 2.65 (95% CI 1.26-5.56) P = .01 and acute GVHD grades II-IV HR 2.23 (95% CI 1.12-4.43) P = .022 were risk factors for nonrelapse mortality in the multivariate analyses. In conclusion, multiple DNA-virus infections are frequent in both haplo-HSCT and UD-HSCT and a risk factor for worse overall survival.

Poor response to hepatitis A vaccination in hematopoietic stem cell transplant recipients.

BACKGROUND: Hepatitis A virus (HAV) infection is highly prevalent in developing countries. In countries experiencing a shift from intermediate/high endemicity to low endemicity, the World Health Organization recommends the incorporation of HAV vaccine into the national vaccination calendar for children aged ≥1 year. Since HAV antibodies wane over time, most HSCT revaccination guidelines advise vaccination as optional, following the country recommendation. However, no study has evaluated the serological response to HAV vaccine in allogeneic HSCT recipients. METHODS: We conducted a prospective study in 46 HSCT recipients who received two doses of inactivated HAV vaccine. Blood samples were taken before vaccination to determine HAV prevalence rates, and before and 4-6 weeks after the second dose. Specific anti-HAV antibodies were detected by a competitive commercial enzyme immune assay. RESULTS: Patients received the first dose of vaccine at a median of 332.5 (120-4134) days after HSCT. Median absolute lymphocyte count at vaccination was 1947 (696-12 500)/mm3 . The seroprevalence rate was 93.5% at inclusion. Although safe and well tolerated, the serological response to HAV vaccine in susceptible patients was poor (33%), and no boost effect was observed in seropositive patients. CONCLUSIONS: In areas with intermediate/high seroprevalence of HAV, serology should be recommended prior to referral to vaccination. The mechanisms of antibody interference and how to overcome T-cell function deficiency need to be better understood in transplant populations receiving HAV vaccine. Alternative schedules of HAV vaccination should be evaluated in prospective trials.

Persistence of Zika Virus in Breast Milk after Infection in Late Stage of Pregnancy.

We detected Zika virus in breast milk of a woman in Brazil infected with the virus during the 36th week of pregnancy. Virus was detected 33 days after onset of signs and symptoms and 9 days after delivery. No abnormalities were found during fetal assessment or after birth of the infant.

Prolonged viremia in dengue virus infection in hematopoietic stem cell transplant recipients and patients with hematological malignancies.

Fever, skin rash, headache, and thrombocytopenia are considered hallmarks of dengue infection. However, these symptoms are frequently observed in infectious and non-infectious complications of hematopoietic stem cell transplant recipients and oncohematological patients. Thus, laboratory confirmation of dengue is relevant for prompt intervention and proper management of dengue in endemic and non-endemic regions. Because no prospective study of dengue has been conducted in these populations, the actual morbidity and mortality of dengue is unknown. In the present series, we describe five cases of dengue in patients living in endemic areas, emphasizing the prolonged course of the disease and the occurrence of prolonged viremia.

Use of Specific T Lymphocytes in Treating Cytomegalovirus Infection in Hematopoietic Cell Transplant Recipients: A Systematic Review.

Cytomegalovirus (CMV) poses a significant threat to post-hematopoietic cell transplantation (HCT). Control strategies include letermovir prophylaxis or ganciclovir pre-emptive therapy (PET). Without prophylaxis, 65-90% of seropositive recipients develop a clinically significant CMV infection. Due to PET drawbacks, letermovir prophylaxis is preferable, as it reduces CMV-related events and improves overall survival. However, refractory or resistant CMV-CS remains a challenge, with maribavir showing limited efficacy. This systematic review followed the Cochrane Manual and PRISMA guidelines and was registered in PROSPERO. Searches were conducted in PubMed, Scopus, Embase, and Web of Science. Out of 1895 identified records, 614 duplicates were removed, and subsequent screening excluded 1153 studies. Eleven included studies (2012-2024) involved 255 HCT recipients receiving adoptive immunotherapy (AI), primarily CMV-specific T-cell therapy. GvHD occurred in 1.82% of cases. Adverse events occurred in 4.4% of cases, while mild CRS was observed in 1.3% of patients. Efficacy, evaluated in 299 patients across eleven studies, showed an average response rate of 78.2%. CMV-CS recurrence was observed in 24.4% of 213 patients, and death due to CMV was reported in 9.7% of 307 patients across nine studies. Adoptive hCMV-specific T-cell immunotherapy appears to be a safe, effective alternative for refractory CMV-CS in HCT.

Assessing the risks for stillbirth in São Paulo, Brazil: protocol for a multidisciplinary case-control study - FetRisks.

Stillbirth is a fundamental component of childhood mortality, but its causes are still insufficiently understood. This study aims to explore stillbirth risk factors by using a multidisciplinary approach to stimulate public policies and protocols to prevent stillbirth, improve maternal care and support bereaved families. METHODS AND ANALYSIS: In this case-control study with stillbirths and live births in 14 public hospitals in São Paulo, mothers are interviewed at hospitals after delivery, and hospital records and prenatal care registries are reviewed. Maternal and umbilical cord blood samples and placentas are collected to analyse angiogenesis and infection biomarkers, and the placenta's anatomopathological exam. Air pollutant exposure is estimated through the participant's residence and work addresses. Traditional and non-invasive autopsies by image-guided histopathology are conducted in a subset of stillbirths. Subsample mothers of cases are interviewed at home 2 months after delivery on how they were dealing with grief. Information contained in the official prenatal care registries of cases and controls is being compiled. Hospital managers are interviewed about the care offered to stillbirth mothers. Data analysis will identify the main risk factors for stillbirth, investigate their interrelations, and evaluate health services care and support for bereaved families. We hope this project will contribute to the understanding of stillbirth's risk factors and related health services in Brazil, providing new knowledge about this central public health problem, contributing to the improvement of public policies and prenatal and puerperal care, helping to prevent stillbirths and improve the healthcare and support for bereaved families. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of the Municipal Health Secretary (process no 16509319.0.3012.5551) and of the Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (process no 16509319.0.0000.0068). Results will be communicated to the study participants, policy-makers and the scientific community.

Respiratory viruses and postoperative hemodynamics in patients with unrestrictive congenital cardiac communications: a prospective cohort study.

BACKGROUND: Pulmonary vascular abnormalities pose a risk for severe life-threatening hemodynamic disturbances following surgical repair of congenital cardiac communications (CCCs). In the distal lung, small airways and vessels share a common microenvironment, where biological crosstalks take place. Because respiratory cells infected by viruses express a number of molecules with potential impact on airway and vascular remodeling, we decided to test the hypothesis that CCC patients carrying viral genomes in the airways might be at a higher risk for pulmonary (and systemic) hemodynamic disturbances postoperatively. METHODS: Sixty patients were prospectively enrolled (age 11 [7-16] months, median with interquartile range). Preoperative pulmonary/systemic mean arterial pressure ratio (PAP/SAP) was 0.78 (0.63-0.88). The presence or absence of genetic material for respiratory viruses in nasopharyngeal and tracheal aspirates was investigated preoperatively in the absence of respiratory symptoms using real-time polymerase chain reaction (kit for detection of 19 pathogens). Post-cardiopulmonary bypass (CPB) inflammatory reaction was analyzed by measuring serum levels of 36 inflammatory proteins (immunoblotting) 4 h after its termination. Postoperative hemodynamics was assessed using continuous recording of PAP and SAP with calculation of PAP/SAP ratio. RESULTS: Viral genomes were detected in nasopharynx and the trachea in 64% and 38% of patients, respectively. Rhinovirus was the most prevalent agent. The presence of viral genomes in the trachea was associated with an upward shift of postoperative PAP curve (p = 0.011) with a PAP/SAP of 0.44 (0.36-0.50) in patients who were positive versus 0.34 (0.30-0.45) in those who were negative (p = 0.008). The presence or absence of viral genomes in nasopharynx did not help predict postoperative hemodynamics. Postoperative PAP/SAP was positively correlated with post-CPB levels of interleukin-1 receptor antagonist (p = 0.026), macrophage migration inhibitory factor (p = 0.019) and monocyte chemoattractant protein-1 (p = 0.031), particularly in patients with virus-positive tracheal aspirates. CONCLUSIONS: Patients with CCCs carrying respiratory viral genomes in lower airways are at a higher risk for postoperative pulmonary hypertension, thus deserving special attention and care. Preoperative exposure to respiratory viruses and post-CPB inflammatory reaction seem to play a combined role in determining the postoperative behavior of the pulmonary circulation.

Endemic or regionally limited bacterial and viral infections in haematopoietic stem-cell transplantation recipients: a Worldwide Network for Blood and Marrow Transplantation (WBMT) Review.

Literature discussing endemic and regionally limited infections in recipients of haematopoietic stem-cell transplantation (HSCT) outside western Europe and North America is scarce. This Worldwide Network for Blood and Marrow Transplantation (WBMT) article is part one of two papers aiming to provide guidance to transplantation centres around the globe regarding infection prevention and treatment, and considerations for transplantation based on current evidence and expert opinion. These recommendations were initially formulated by a core writing team from the WBMT and subsequently underwent multiple revisions by infectious disease experts and HSCT experts. In this paper, we summarise the data and provide recommendations on several endemic and regionally limited viral and bacterial infections, many of which are listed by WHO as neglected tropical diseases, including Dengue, Zika, yellow fever, chikungunya, rabies, brucellosis, melioidosis, and leptospirosis.

Endemic or regionally limited parasitic and fungal infections in haematopoietic stem-cell transplantation recipients: a Worldwide Network for Blood and Marrow Transplantation (WBMT) Review.

There is a scarcity of data on endemic and regionally limited fungal and parasitic infections in recipients of haematopoietic stem-cell transplantation (HSCT) outside western Europe and North America. This Worldwide Network for Blood and Marrow Transplantation (WBMT) Review is one of two papers aiming to provide guidance to transplantation centres worldwide regarding prevention, diagnosis, and treatment based on the currently available evidence and expert opinion. These recommendations were created and reviewed by physicians with expertise in HSCT or infectious disease, representing several infectious disease and HSCT groups and societies. In this paper, we review the literature on several endemic and regionally limited parasitic and fungal infections, some of which are listed as neglected tropical diseases by WHO, including visceral leishmaniasis, Chagas disease, strongyloidiasis, malaria, schistosomiasis, histoplasmosis, blastomycosis, and coccidioidomycosis.

Latent and active tuberculosis infection in allogeneic hematopoietic stem cell transplant recipients: a prospective cohort study.

Tuberculosis (TB) is a major infectious complication in hematopoietic stem cell transplant (HSCT) recipients in countries with high TB prevalence. Identifying and treating latent tuberculosis infection (LTBI) helps to prevent TB reactivation after transplantation. Few studies have compared the tuberculin skin test (TST) with interferon Gamma release assays (IGRA) to diagnose LTBI in HSCT candidates. We compared TST and QuantiFeron TB gold in tube (QTF-GIT) and prospectively evaluated the incidence of active tuberculosis in 126 HSCT candidates and 58 HSCT recipients with chronic GVHD followed at the outpatient clinic. TB was diagnosed by culture in Mycobacteria media and by commercial real-time PCR kit. Considering the positivity of any test, the prevalence of LTBI was 8.7% in HSCT candidates (11 out of 126) and 12.5% in HSCT recipients with chronic GVHD (6 out of 48). QTF-GIT indeterminate results were detected in 2.4% of the HSCT candidates. Fair to good agreement (K > 0.50) between tests was observed in both cohorts. Cumulative incidence of TB was 3% in the GVHD cohort. TB was diagnosed in 2 chronic GVHD recipients, both cases confirmed by positive culture and PCR. None of the 11 patients with LTBI diagnosed pre-HSCT who received INH prophylaxis developed TB.

Influenza virus vaccination in kidney transplant recipients: serum antibody response to different immunosuppressive drugs.

INTRODUCTION: This study prospectively accessed the immune response to the inactivated influenza vaccine in renal transplant recipients receiving either azathioprine or mycophenolate mofetil (MMF). Side effects were investigated. METHODS: Sixty-nine patients received one dose of inactivated trivalent influenza vaccine. Antihemagglutinin (HI) antibody response against each strain was measured before and one to six months after vaccination. RESULTS: Geometric mean HI antibody titers for H1N1 and H3N2 strains increased from 2.57 and 2.44 to 13.45 (p = 0.001) and 7.20 (p < 0.001), respectively. Pre- and post-vaccination protection rates for H1N1 and H3N2 increased from 8.7% to 49.3% (p < 0.001); and 36.3% (p < 0.001) and seroconversion rates were 36% and 25.3%, respectively. There was no response to influenza B. The use of MMF reduced the H1N1 and H3N2 protection rates and the seroconversion rate for the H1N1 strain when compared with the use of azathioprine, and subjects transplanted less than 87 months also had inferior antibody response. Adverse events were mild and there were no change on renal function post-vaccination. CONCLUSION: Renal transplant patients vaccinated against influenza responded with antibody production for influenza A virus strains, but not for influenza B. Use of MMF and shorter time from transplantation decreased the immune response to the vaccine.

Influenza A and B in a cohort of outpatient children and adolescent with influenza like-illness during two consecutive influenza seasons.

INTRODUCTION: Influenza is an important cause of morbimortality worldwide. Although people at the extremes of age have a greater risk of complications, influenza has been more frequently investigated in the elderly than in children, and inpatients than outpatients. Yearly vaccination with trivalent or quadrivalent vaccines is the main strategy to control influenza. OBJECTIVES: Determine the clinical and molecular characteristics of influenza A and B infections in children and adolescents with influenza-like illness (ILI). METHODS: A cohort of outpatient children and adolescents with ILI was followed for 20 months. Influenza was diagnosed with commercial multiplex PCR platforms. RESULTS: 179 patients had 277 episodes of ILI, being 79 episodes of influenza A and 20 episodes of influenza B. Influenza A and B cases were mild and had similar presentation. Phylogenetic tree of influenza B viruses showed that 91.6% belonged to the B/Yamagata lineage, which is not included in trivalent vaccines. CONCLUSIONS: Influenza A and B are often detected in children and adolescents with ILI episodes, with similar and mild presentation in outpatients. The mismatch between the circulating influenza viruses and the trivalent vaccine offered in Brazil may have contributed to the high frequency of influenza A and B in this population.

Molecular characterization of strains of respiratory syncytial virus identified in a hematopoietic stem cell transplant outpatient unit over 2 years: community or nosocomial infection?

Respiratory syncytial virus (RSV) is recognized as the leading cause of nosocomial respiratory infection among hematopoietic stem cell transplant (HSCT) recipients, causing considerable morbidity and mortality. RSV is easily transmitted by contact with contaminated surfaces, and in HSCT units, more than 50% of RSV infections have been characterized as of nosocomial origin. From April 2001 to October 2002, RSV was identified by direct immunofluorescent assay in 42 symptomatic HSCT recipients. Seven RSV strains from 2001 and 12 RSV strains from 2002 were sequenced. RNA extraction, cDNA synthesis, and seminested polymerase chain reaction (PCR) with primers complementary to RSV genes G and F were performed. PCR products were analyzed by nucleotide sequencing of the C-terminal region of gene G for typing (in group A or B). Of the 7 strains analyzed in 2001, only 2 belonged to group B; the other 5 belonged to group A. Of these 7 strains, 3 were identical and were from recipients receiving outpatient care. In 2002, of the 12 strains analyzed, 3 belonged to group A and the other 9 belonged to group B. Of these 9 strains, 7 were genetically identical and were also from recipients receiving outpatient care. Therefore, multiple strains of RSV cocirculated in the hematopoietic stem cell transplant units (ward and outpatient units) between 2001 and 2002. Nosocomial transmission was more likely to occur at the HSCT outpatient unit than in the HSCT ward. Infection control practices should also be implemented in the outpatient setting.

Thymopoiesis in Pre- and Post-Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) is an important therapeutic option for some hematological diseases. However, patients who undergo HSCT acquire a state of immunodeficiency that causes significant mortality. Reconstitution of thymic function is needed to support the immune system. One way to measure thymic function is through T-cell receptor excision circle (TREC) quantification. TRECs are generated by T-cell receptor gene rearrangements during T-cell maturation in the thymus and represent a reliable marker for thymic output. In this study, we aimed to assess aging and malignant hematological diseases as two important factors that may influence thymic output before HSCT. We observed that patients before HSCT presented signal joint TREC (sjTREC) numbers lower than 606.55 copies/µg DNA (low values) compared with healthy individuals, with an odds ratio (OR) of 12.88 [95% confidence interval (CI): 5.26-31.53; p < 0.001]. Our results showed that a group of older individuals (≥50 years old), comprising both healthy individuals and patients, had an OR of 10.07 (95% CI: 2.80-36.20) for low sjTREC values compared with younger individuals (≤24 years old; p < 0.001). Multiple logistic regression analysis confirmed that both older age (≥50 years old) and malignant hematological diseases and their treatments were important and independent risk factors related to thymic function impairment (p < 0.001). The median sjTREC value for patients of all ages was significantly lower than the sjTREC median for the subgroup of older healthy individuals (≥50 years old; p < 0.001). These data suggested that patients before HSCT and healthy individuals exhibited age-dependent thymic impairment, and that prior treatment for hematological diseases may exacerbate aging-related deterioration of natural thymic function. Furthermore, we analyzed these patients 9 months post-HSCT and compared patients who underwent autologous HSCT with those who underwent allogeneic HSCT. Both groups of patients achieved sjTREC copy numbers similar to those of healthy individuals. We did not find a close relationship between impaired thymic function prior to HSCT and worse thymic recovery after HSCT.

Attitudes of health care workers to influenza vaccination: why are they not vaccinated?

BACKGROUND: Compliance rates with influenza vaccination among health care workers (HCW) are historically low. Although a safe and effective vaccine is available, the reasons for such poor compliance are not well understood. METHODS: After a campaign encouraging HWC to vaccinate against influenza, we conducted an epidemiologic survey to evaluate the reasons for compliance and accompanied the impact of these measures (campaign and questionnaire) during the subsequent 2 years. RESULTS: Compliance rate was 34.4%. Multivariate analysis showed that "older age" (P = .008), "believing that most departmental colleagues had been vaccinated" (P < .0001), and "having cared for patients suffering from severe influenza" (P = .031) were significantly associated with compliance with influenza vaccination. The main reason given for being vaccinated was "individual protection" and, to a lesser extent, "protection for the patient." In subsequent years, compliance rates among those participating in the survey fell to 20.2% in 2004, when the only measure taken was the questionnaire, and to 12.75% in 2005, when no educational intervention was scheduled. CONCLUSION: We conclude that a better understanding of HCW's negative attitude regarding influenza vaccination is needed as are more appealing and convincing continuous education programs, to ensure motivation for influenza vaccination over a longer period.

Effectiveness of influenza vaccination of schoolchildren in the city of São Paulo, Brazil, 2009.

BACKGROUND: Children play an important role in maintaining the transmission of influenza. Evidence suggests that vaccination of school-age children can reduce transmission to unvaccinated household contacts. We evaluated the direct and indirect effectiveness of the 2009 inactivated seasonal influenza vaccine in vaccinated schoolchildren and their unvaccinated household contacts. METHODS: This was a double-blind cluster randomized trial involving 10 schools and 1742 schoolchildren as well as 5406 household contacts. The schools were randomly assigned to receive the influenza vaccine or the control vaccine. After vaccination, the schoolchildren and household contacts were followed for 6 months to identify cases of acute respiratory infection (ARI). Reverse-transcriptase polymerase chain reaction was performed for the diagnosis of influenza. RESULTS: A total of 632 ARI cases were detected. Of those, 103 tested positive for influenza virus (influenza virus A[H1N1]pdm09 virus in 55 and seasonal influenza viruses in 48). The effectiveness of the vaccine in protecting against seasonal influenza virus infection was 65·0% for the household contacts (95% CI, 19·6-84·3) and 65·0% for the schoolchildren (95% CI, 20·9-84·5). CONCLUSION: Vaccination of schoolchildren significantly protected them and their household contacts against seasonal influenza.

Influenza A and B in a cohort of outpatient children and adolescent with influenza like-illness during two consecutive influenza seasons

ABSTRACT Introduction Influenza is an important cause of morbimortality worldwide. Although people at the extremes of age have a greater risk of complications, influenza has been more frequently investigated in the elderly than in children, and inpatients than outpatients. Yearly vaccination with trivalent or quadrivalent vaccines is the main strategy to control influenza. Objectives Determine the clinical and molecular characteristics of influenza A and B infections in children and adolescents with influenza-like illness (ILI). Methods: A cohort of outpatient children and adolescents with ILI was followed for 20 months. Influenza was diagnosed with commercial multiplex PCR platforms. Results: 179 patients had 277 episodes of ILI, being 79 episodes of influenza A and 20 episodes of influenza B. Influenza A and B cases were mild and had similar presentation. Phylogenetic tree of influenza B viruses showed that 91.6% belonged to the B/Yamagata lineage, which is not included in trivalent vaccines. Conclusions: Influenza A and B are often detected in children and adolescents with ILI episodes, with similar and mild presentation in outpatients. The mismatch between the circulating influenza viruses and the trivalent vaccine offered in Brazil may have contributed to the high frequency of influenza A and B in this population.