Safety of the yellow fever vaccine in people living with HIV: a longitudinal study exploring post-vaccination viremia and hematological and liver kinetics.

BACKGROUND: Safety data on the yellow fever vaccine 17DD in People Living with HIV (PLWH) are limited. This study explored the occurrence of post-vaccination 17DD viremia and the kinetics of hematological and liver laboratorial parameters in PLWH and HIV-uninfected participants [HIV(-) controls]. METHODS: We conducted a secondary analysis of a longitudinal interventional trial (NCT03132311) study that enrolled PLWH and HIV(-) controls to receive a single 17DD dose and were followed at 5, 30 and 365 days after vaccination in Rio de Janeiro, Brazil. 17DD viremia (obtained throughreal-time PCR and plaque forming units' assays), hematological (neutrophils, lymphocytes and platelets counts) and liver enzymes (ALT and AST) results were assessed at baseline and Days 5 and 30 post-vaccination. Logistic regression models explored factors associated with the odds of having positive 17DD viremia. Linear regression models explored variables associated with hematological and liver enzymes results at Day 5. RESULTS: A total of 202 PLWH with CD4 ≥ 200 cells/µL and 68 HIV(-) controls were included in the analyses. 17DD viremia was found in 20.0 % of the participants and was twice more frequent in PLWH than in HIV(-) controls (22.8% vs. 11.8 %, p-value < 0.001). Neutrophils, lymphocytes and platelets counts dropped at Day 5 and returned to baseline values at Day 30. 17DD viremia was associated with lower nadir of lymphocytes and platelets at Day 5. ALT levels did not increase post-vaccination and were not associated with 17DD viremia. CONCLUSIONS: 17DD was safe and well-tolerated in PLWH with CD4 ≥ 200 cells/µL. Post-vaccination viremia was more frequent in PLWH than in controls. Transient and self-limited decreases in lymphocytes and neutrophils occurred early after vaccination. 17DD viremia was associated with lower lymphocytes and platelets nadir after vaccination. We did not observe elevations in ALT after 17DD vaccination.

Safety of the yellow fever vaccine in people living with HIV: a longitudinal study exploring post-vaccination viremia and hematological and liver kinetics

ABSTRACT Background: Safety data on the yellow fever vaccine 17DD in People Living with HIV (PLWH) are limited. This study explored the occurrence of post-vaccination 17DD viremia and the kinetics of hematological and liver laboratorial parameters in PLWH and HIV-uninfected participants [HIV(-) controls]. Methods: We conducted a secondary analysis of a longitudinal interventional trial (NCT03132311) study that enrolled PLWH and HIV(-) controls to receive a single 17DD dose and were followed at 5, 30 and 365 days after vaccination in Rio de Janeiro, Brazil. 17DD viremia (obtained throughreal-time PCR and plaque forming units' assays), hematological (neutrophils, lymphocytes and platelets counts) and liver enzymes (ALT and AST) results were assessed at baseline and Days 5 and 30 post-vaccination. Logistic regression models explored factors associated with the odds of having positive 17DD viremia. Linear regression models explored variables associated with hematological and liver enzymes results at Day 5. Results: A total of 202 PLWH with CD4 > 200 cells/μL and 68 HIV(-) controls were included in the analyses. 17DD viremia was found in 20.0 % of the participants and was twice more frequent in PLWH than in HIV(-) controls (22.8% vs. 11.8 %, p-value < 0.001). Neutrophils, lymphocytes and platelets counts dropped at Day 5 and returned to baseline values at Day 30. 17DD viremia was associated with lower nadir of lymphocytes and platelets at Day 5. ALT levels did not increase post-vaccination and were not associated with 17DD viremia. Conclusions: 17DD was safe and well-tolerated in PLWH with CD4 > 200 cells/μL. Post-vaccination viremia was more frequent in PLWH than in controls. Transient and self-limited decreases in lymphocytes and neutrophils occurred early after vaccination. 17DD viremia was associated with lower lymphocytes and platelets nadir after vaccination. We did not observe elevations in ALT after 17DD vaccination.

Immunogenicity and reactogenicity of yellow fever vaccine in people with HIV.

OBJECTIVE: To evaluate immunogenicity and reactogenicity of yellow fever (YF) vaccine in people with HIV (PWH) compared to HIV-uninfected controls. DESIGN: In this longitudinal interventional trial (NCT03132311), PWH with CD4 + cell count ≥200 cells/µl and controls, aged 18-59, without a previous history of YF vaccination received a single standard dose of YF vaccine (17DD) and were followed at Days 5, 30 and Year 1. METHODS: YF-neutralization titers were measured at Days 0, 30 and Year 1 and geometric mean titers (GMT) were calculated. Adverse events (AE) and YF virus detection were measured at Days 5 and 30. Linear regression evaluated factors associated with YF-neutralization titers. RESULTS: Two hundred and eighteen PWH and 82 controls were included. At baseline, all PWH were using antiretroviral therapy; 92.6% had undetectable HIV viral load (VL) and median CD4 + cell count was 630 cells/µl [interquartile range (IQR) 463-888]. YF vaccine was safe and there were no serious AEs. At Day 30, seroconversion was observed in 98.6% of PWH [95% confidence interval (CI): 95.6-99.6] and in 100% of controls (95% CI: 93.9-100); at Year 1, 94.0% of PWH (95% CI: 89.6-96.7) and 98.4% of controls (95% CI 90.3-99.9) were seropositive. PWH had lower GMTs than controls at Day 30 and Year 1. Baseline VL >1000 copies/ml, low CD4 + cell count and low CD4 + /CD8 + ratio were associated with lower YF-neutralization titers. CONCLUSIONS: YF vaccine is safe in PWH with CD4 + cell count ≥200 cells/µl. YF vaccine immunogenicity is impaired in PWH, particularly among those with high VL, low CD4 + cell count and low CD4 + /CD8 + ratio at vaccination and YF-neutralization titers decays over time.

Impact and Effectiveness of 10 and 13-Valent Pneumococcal Conjugate Vaccines on Hospitalization and Mortality in Children Aged Less than 5 Years in Latin American Countries: A Systematic Review.

BACKGROUND: Several Latin American and Caribbean (LAC) countries have introduced pneumococcal conjugate vaccine (PCV-10 or PCV-13) in their routine national immunization programs. OBJECTIVES: We aimed to summarize the evidence of PCV impact and effectiveness in children under 5 years old in the LAC Region. METHODS: We conducted a systematic review of the literature on impact or effectiveness of PCVs on deaths or hospitalizations due to invasive pneumococcal disease (IPD), pneumonia, meningitis and sepsis. We searched Medline, WoS, Lilacs, Scopus, Central and gray literature published in any language from 2009 to January 2016. We included studies addressing the outcomes of interest in children in the target age group, and with the following designs: randomized trials, cohort or case-control, interrupted time series with at least three data points before and after the intervention, and before-after studies. Screening of citations, data extraction, and risk of bias assessment were conducted in duplicate by independent reviewers, according to the study protocol registered on PROSPERO. Descriptive analysis of the effectiveness measurements and sensitivity analysis were conducted. Effectiveness is reported as 1-OR or 1-RR for case control or cohort/clinical trials, and as percent change of disease incidence rates for before-after studies. RESULTS: We identified 1,085 citations, 892 from databases and 193 from other sources. Of these, 22 were further analyzed. Studies were from Brazil, Chile, Uruguay, Argentina, Peru and Nicaragua. Effectiveness ranged from 8.8-37.8% for hospitalizations due to X-ray confirmed pneumonia, 7.4-20.6% for clinical pneumonia, and 13.3-87.7% for meningitis hospitalizations, and 56-83.3% for IPD hospitalization, varying by age, outcome definition, type of vaccine and study design. CONCLUSIONS: Available evidence to date indicates significant impact of both PCV-10 and PCV-13 in the outcomes studied, with no evidence of the superiority of one vaccine over the other on pneumonia, IPD or meningitis hospitalization reduction in children under 5 years old.

X ray screening at entry and systematic screening for the control of tuberculosis in a highly endemic prison.

BACKGROUND: Tuberculosis (TB) is a major issue in prisons of low and middle income countries where TB incidence rates are much higher in prison populations as compared with the general population. In the Rio de Janeiro (RJ) State prison system, the TB control program is limited to passive case-finding and supervised short duration treatment. The aim of this study was to measure the impact of X-ray screening at entry associated with systematic screening on the prevalence and incidence of active TB. METHODS: We followed up for 2 years a RJ State prison for adult males (1429 inmates at the beginning of the study) and performed, in addition to passive case-finding, 1) two "cross-sectional" X-ray systematic screenings: the first at the beginning of the study period and the second 13 months later; 2) X-ray screening of inmates entering the prison during the 2 year study period. Bacteriological examinations were performed in inmates presenting any pulmonary, pleural or mediastinal X-ray abnormality or spontaneously attending the prison clinic for symptoms suggestive of TB. RESULTS: Overall, 4326 X-rays were performed and 246 TB cases were identified. Prevalence among entering inmates remained similar during 1st and the 2nd year of the study: 2.8% (21/754) and 2.9% (28/954) respectively, whereas prevalence decreased from 6.0% (83/1374) to 2.8% (35/1244) between 1st and 2nd systematic screenings (p < 0.0001). Incidence rates of cases identified by passive case-finding decreased from 42 to 19 per 1000 person-years between the 1st and the 2nd year (p < 0.0001). Cases identified by screenings were less likely to be bacteriologically confirmed as compared with cases identified by passive-case finding. CONCLUSIONS: The strategy investigated, which seems highly effective, should be considered in highly endemic confined settings such as prisons.

17DD yellow fever vaccine: a double blind, randomized clinical trial of immunogenicity and safety on a dose-response study.

OBJECTIVE: To verify if the Bio-Manguinhos 17DD yellow fever vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation. RESULTS: Doses from 27,476 IU to 587 IU induced similar seroconversion rates and neutralizing antibodies geometric mean titers (GMTs). Immunity of those who seroconverted to YF was maintained for 10 mo. Reactogenicity was low for all groups. METHODS: Young and healthy adult males (n = 900) were recruited and randomized into 6 groups, to receive de-escalating doses of 17DD-YFV, from 27,476 IU to 31 IU. Blood samples were collected before vaccination (for neutralization tests to yellow fever, serology for dengue and clinical chemistry), 3 to 7 d after vaccination (for viremia and clinical chemistry) and 30 d after vaccination (for new yellow fever serology and clinical chemistry). Adverse events diaries were filled out by volunteers during 10 d after vaccination. Volunteers were retested for yellow fever and dengue antibodies 10 mo later. Seropositivity for dengue was found in 87.6% of volunteers before vaccination, but this had no significant influence on conclusions. CONCLUSION: In young healthy adults Bio-Manguinhos/Fiocruz yellow fever vaccine can be used in much lower doses than usual. INTERNATIONAL REGISTER: ISRCTN 38082350.

Evaluation of accuracy and reliability of the plaque reduction neutralization test (micro-PRNT) in detection of yellow fever virus antibodies.

Yellow fever is a disease caused by the prototype virus of the genus Flavivirus and remains endemic in tropical forest regions from Africa and South America, despite the availability of effective vaccines. These are capable of inducing a rapid specific immune response, with the formation of neutralizing antibodies that appear early, are protective and long lasting. The Plaque Reduction Neutralization Test is considered the most sensitive and specific test for quantification of neutralizing antibodies, and the reference method for assessing the protective immune response after vaccination. This study evaluated the reliability (repeatability and reproducibility) and accuracy (sensitivity, specificity and overall accuracy) of micro-PRNT50 and compared its performance with the micro-PRNT90. Although the micro-PRNT50 has showed satisfactory levels of reliability (ICCs ranged from 0.62 to 0.NorNormas e Manuais Técnicosas e Manuais Técnicos6 for repeatability and 0.72 for reproducibility) and accuracy (sensitivity of 91.1%, specificity of 72.9% and overall accuracy of 78%), the micro-PRNT90 showed higher performance, with ICCs for repeatability ranged from 0.78 to 0.79 and 0.81 for reproducibility, sensitivity of 100%, specificity of 94.7% and overall accuracy of 95%. Modifications in the test methodology and changes in the classification criteria in the readings of the results obtained will be important to improve the accuracy of micro-PRNT.

Impact of PGL-I seropositivity on the protective effect of BCG vaccination among leprosy contacts: a cohort study.

BACKGROUND: Contacts of leprosy patients are at increased risk of developing leprosy and need to be targeted for early diagnosis. Seropositivity to the phenolic glycolipid I (PGL-I) antigen of Mycobacterium leprae has been used to identify contacts who have an increased risk of developing leprosy. In the present study, we studied the effect of seropositivity in patient contacts, on the risk of developing leprosy, stratified by Bacille Calmette Guerin (BCG) vaccination after index case diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: Leprosy contacts were examined as part of the surveillance programme of the Oswaldo Cruz Institute Leprosy Outpatient Clinic in Rio de Janeiro. Demographic, social, epidemiological and clinical data were collected. The presence of IgM antibodies to PGL-I in sera and BCG vaccination status at the time of index case diagnosis were evaluated in 2,135 contacts. During follow-up, 60 (2.8%; 60/2,135) leprosy cases were diagnosed: 41 among the 1,793 PGL-I-negative contacts and 19 among the 342 PGL-I-positive contacts. Among PGL-I-positive contacts, BCG vaccination after index case diagnosis increased the adjusted rate of developing clinical manifestations of leprosy (Adjusted Rate Ratio (aRR) = 4.1; 95% CI: 1.8-8.2) compared with the PGL-I-positive unvaccinated contacts (aRR = 3.2; 95% CI: 1.2-8.1). The incidence density was highest during the first year of follow-up for the PGL-I-positive vaccinated contacts. However, all of those contacts developed PB leprosy, whereas most MB cases (4/6) occurred in PGL-I-positive unvaccinated contacts. CONCLUSION: Contact examination combined with PGL-I testing and BCG vaccination remain important strategies for leprosy control. The finding that rates of leprosy cases were highest among seropositive contacts justifies targeting this specific group for close monitoring. Furthermore, it is recommended that PGL-I-positive contacts and contacts with a high familial bacteriological index, regardless of serological response, should be monitored. This group could be considered as a target for chemoprophylaxis.

Mutual interference on the immune response to yellow fever vaccine and a combined vaccine against measles, mumps and rubella.

A randomized trial was conducted to assess the immunogenicity and reactogenicity of yellow fever vaccines (YFV) given either simultaneously in separate injections, or 30 days or more after a combined measles-mumps-rubella (MMR) vaccine. Volunteers were also randomized to YFV produced from 17DD and WHO-17D-213 substrains. The study group comprised 1769 healthy 12-month-old children brought to health care centers in Brasilia for routine vaccination. The reactogenicity was of the type and frequency expected for the vaccines and no severe adverse event was associated to either vaccine. Seroconversion and seropositivity 30 days or more after vaccination against yellow fever was similar across groups defined by YFV substrain. Subjects injected YFV and MMR simultaneously had lower seroconversion rates--90% for rubella, 70% for yellow fever and 61% for mumps--compared with those vaccinated 30 days apart--97% for rubella, 87% for yellow fever and 71% for mumps. Seroconversion rates for measles were higher than 98% in both comparison groups. Geometric mean titers for rubella and for yellow fever were approximately three times higher among those who got the vaccines 30 days apart. For measles and mumps antibodies GMTs were similar across groups. MMR's interference in immune response of YFV and YFV's interference in immune response of rubella and mumps components of MMR had never been reported before but are consistent with previous observations from other live vaccines. These results may affect the recommendations regarding primary vaccination with yellow fever vaccine and MMR.

Yellow fever vaccination: some thoughts on how much is enough [Vaccine 23 (2005) 3908-3914].

In a recently published article in this journal, Massad et al. contraindicates yellow fever vaccination to persons 60 years or older, considering that the risk of serious adverse events is higher for this age class. The conclusion was based on the input of available data on age-related probabilities of developing serious adverse events in the United States, as well on other data not firmly established. We consider such contraindication inadequate, because the data input has limitations, higher letality of wild-type yellow fever infection in older adults, risk of introduction of yellow fever by travelers into new countries, lower risk of vaccine adverse events in revaccinated or immune people in endemic countries, and the experience of Brazil, with only one suspect case of associated viscerotropic disease in an individual older than 60 years. The model proposed by Massad et al. is useful but can lead to different conclusions, depending on the epidemiological context and individual risk profile.

Influenza vaccination in Brazil: rationale and caveats

Campanhas de vacinação contra influenza na população idosa têm sido conduzidas no Brasil desde 1999. De acordo com levantamento da literatura realizada sobre influenza no Brasil, concluiu-se que dados sobre carga de doença são ainda escassos e imprecisos. Essas informações parecem indicar que a vacinação tem produzido algum impacto nas regiões Sul e Sudeste do País, mas não em outras regiões. Foram discutidas racionalidade técnica e científica para a imunização contra influenza, e argumentou-se que a atual estratégia de vacinação em todo o território nacional não levou em conta possíveis diferenças na ocorrência da doença causada por influenza entre as regiões do País. Foram sugeridas algumas atividades relacionadas à vigilância epidemiológica de influenza que se julgou necessárias para responder importantes questões referentes à vacinação e seu impacto no Brasil.

Influenza vaccination in Brazil: rationale and caveats.

Mass vaccination campaigns against influenza in the elderly have been conducted in Brazil since 1999. A search of the literature on influenza in Brazil indicated that data on disease burden are still scarce and inaccurate. Published data seem to indicate that vaccination has produced some impact in the southern and southeastern regions but not in other regions of Brazil. A discussion of the technical and scientific rationale for mass immunization against influenza is presented and it is argued that the current strategy has not taken into account potential differences in disease occurrence in different areas. It is suggested some epidemiological surveillance actions needed to address major concerns regarding mass influenza vaccination and its impact in Brazil.

Estudo de soroconversäo com formulaçöes da vacina Biken CAM-70 contra sarampo / Comparison of seroconversion rates with CAM-70 measles vaccine at different dosages

Objetivo: Comparar a resposta sorológica induzida por formulaçöes com diferentes concentraçöes de vírus da vacina contra sarampo da cepa Biken CAM-70. Métodos: Crianças sadias de 9 a 18 meses de um centro de saúde do Rio de Janeiro, RJ, cujos responsáveis concordaram em participar, foram randomizadas em três grupos vacinados com concentraçöes de 5.000, 1.000 ou 200 CCID50 (50 por cento Tissue Culture Infective Dose). Os participantes e o pessoal da pesquisa ignoravam o tipo de vacina administrada. A avaliaçäo sorológica foi realizada pelo teste de reduçäo em plaque de lise. Duas análises intermediárias dos dados foram programadas. Resultados: Das 223 crianças recrutadas, 84 por cento completaram todos os procedimentos; 79 por cento tinham idade menor que 10 meses; 93 por cento näo tinham anticorpos contra sarampo no soro pré-vacinal. As proporçöes de soroconversäo (quadruplicaçäo das concentraçöes pré-vacinais) foram 82 por cento, 55 por cento e 37 por cento (p<0,0000), nos grupos vacinados com 5.000, 1.000 ou 200 CCID50, respectivamente. As diferenças nas concentraçöes médias de anticorpos pós-vacinais também foram substanciais e estatisticamente significativas (p<0,000). A soroconversäo (independente da formulaçäo da vacina) foi de 73 por cento nas crianças com 10 ou mais meses de idade e 53 por cento naquelas com menos de 10 meses. Conclusöes: Formulaçöes da vacina com concentraçöes inferiores a 5.000 CCID50 näo induziram soroconversäo satisfatória. O desempenho da vacina por faixa etária foi compatível com o observado em outros estudos com a vacina Biken CAM-70 e indica que uma proporçäo apreciável de crianças vacinadas aos 9 meses pode näo obter resposta imunológica plena

Historia natural del bloqueo auriculoventricular de tercer grado en la miocarditis chagásica crónica / Natural history of the auriculoventricular block of third grade in the chronic chagasic myocarditis

Presenta un estudio basado en la revisión de 380 electrocardiogramas de 103 enfermos con miocarditis chagásica crónica y bloqueo auriculaventricular de tercer grado, 93 de los cuales fallecieron por insuficiencia cardíaca, arritmias graves y paro cardíaco. Se busca una posible explicación para la larga supervivencia observada, agrupándose a los enfermos fallecidos, en tres grupos, según hayan tenido una sobrevida de entre 3 meses a 5 años, de 5 a 20 años, y, de 20 a 30 o más; observándose en los enfermos restantes una sobrevida de entre 8 meses y 16 años, con 5 meses de evolución. Se observaron tres fases en el tiempo de sobrevida de los enfermos: una, inicial, que puede corresponder a las primeras semanas o meses de asistencia médica; una segun da, media, en que se presentan síntomas variables y algunas limitaciones en la actividad de los enfermos, y, la final, en que se apresentan síntomas importantes y se requiere hospitalización. Analiza ejemplos de alteraciones electrocardiográficas en las distintas fases de evolución y los possibles mecanismos idioventriculares de comandos y de escapas en cada una de las combinaciones de morfología de bloqueos