Corrigendum: Duration of Humoral and Cellular Immunity 8 Years After Administration of Reduced Doses of the 17DD-Yellow Fever Vaccine.

[This corrects the article DOI: 10.3389/fimmu.2019.01211.].

Duration of Humoral and Cellular Immunity 8 Years After Administration of Reduced Doses of the 17DD-Yellow Fever Vaccine.

The present study aims to determine whether 17DD-YF-specific humoral and cellular immunological memory is maintained 8-years after primary vaccination with subdoses (10,447IU;3,013IU;587IU;158IU;31IU). For this purpose, this follow-up study was carried out in a subset of volunteers (n = 98) originally enrolled in the dose-response study in 2009 and 46 non-vaccinated controls. Our results demonstrated that vaccinees, who had seroconverted following primary vaccination and had not been revaccinated, present similar neutralizing antibodies levels and YF-specific cellular memory, particularly CMCD4 and EMCD8 as compared to the reference full dose (27,476IU). Although, PRNT seropositivity rates were similar across subgroups (94, 82, 83, 94, 80, and 91%, correspondingly), only doses above 587IU elicited similar iterative proportion of seropositivity rates, calculated as a progressive decrease on seropositivity rates along time (89, 80, 80, and 91%, respectively) as compared to 158IU and 31IU (68 and 46%, respectively). Noteworthy were the strong positive correlations ("EMCD4,EMCD8" and "TNFCD8,IFNCD8") observed in most subdoses, except for 31IU. Major similarities underscored the preserved antibody titers and the outstanding levels of EMCD8, relevant correlates of protection for YF-specific immunity. These findings provide evidences to support the regular use of dose sparing strategy for YF vaccine in adults.

Duration of post-vaccination immunity to yellow fever in volunteers eight years after a dose-response study.

In 2009, Bio-Manguinhos conducted a dose-response study with the yellow fever vaccine, administering the vaccine in the usual mean dose of 27,476 IU (full dose, reference) and in tapered doses (10,447 IU, 3013 IU, 587 IU, 158 IU, and 31 IU) by the usual subcutaneous route and usual volume (0.5 mL). Tapered doses were obtained by dilution in the manufacturer's laboratory, and the test batches presented industrial quality. Doses down to 587 IU showed similar immunogenicity to the full dose (27,476, reference), while the 158 IU and 31 IU doses displayed lower immunogenicity. Seropositivity was maintained at 10 months, except in the group that received the 31 IU dose. The current study aims to determine whether yellow fever seropositivity was maintained eight years after YF vaccination in non-revaccinated individuals. According to the current study's results, seropositivity was maintained in 85% of 318 participants and was similar across groups. The findings support the use of the yellow fever vaccine in fractional doses during outbreaks, but each fractional dose should have at least 587 IU. This study also supports the minimum dose required by WHO, 1000 IU. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov NCT 03338231.

Pharmacokinetics comparison of two pegylated interferon alfa formulations in healthy volunteers.

BACKGROUND: Several countries have used pegylation technology to improve the pharmacokinetic properties of essential drugs. Recently, a novel interferon alfa-2b protein conjugated to four-branched 12 kDa polyethylene glycol molecules was developed jointly between Cuba and Brazil. The aim of this study was to compare the pharmacokinetic properties of BIP48 (pegylated interferon alfa-2b from Bio-Manguinhos/Fiocruz, Brazil) to those of PEGASYS® (commercially available pegylated interferon alfa-2a from Roche Pharmaceutical). METHODS: This phase I, single-centre, randomized, double-blind crossover trial enrolled 31 healthy male volunteers aged 19 to 35 who were allocated to two stages, either side of a 5-week wash-out period, with each arm lasting 14 consecutive days after subcutaneous administration of 180 µg of one formulation or the other (study or comparator). The main outcome variable was serum pegylated interferon concentrations in 15 samples collected during the course of the study and tested using an enzyme immunoassay. RESULTS: There were no differences between formulations in terms of magnitude or absorption parameters. Analysis of time parameters revealed that BIP48 remained in the body significantly longer than PEGASYS® (Tmax: 73 vs. 54 h [p = 0.0010]; MRT: 133 vs. 115 h [p = 0.0324]; ke: 0.011 vs. 0.013 h(-1) [p = 0.0153]; t1/2: 192 vs. 108 h [p = 0.0218]). CONCLUSION: BIP48 showed the expected pharmacokinetic profile for a pegylated product with a branched molecular structure. Compared to PEGASYS®, the magnitude absorption was similar, but time parameters were consistent with slower elimination. Further studies should be conducted to evaluate the clinical implications of these findings. A phase II-III repeated-dose clinical trial is ongoing to study these findings in patients with chronic hepatitis C virus infection. TRIAL REGISTRATION: This study is registered on the ClinicalTrials.gov platform (accession number NCT01889849 ). This trial was retrospectively registered in June 2013.

Immunogenicity and safety of measles-mumps-rubella vaccine delivered by disposable-syringe jet injector in healthy Brazilian infants: a randomized non-inferiority study.

This study aimed to determine if immunogenicity to measles-mumps-rubella vaccine delivered to infants via a disposable-syringe jet injector (DSJI) was non-inferior to that administered by needle and syringe (NS). Vaccination safety was evaluated, as were the use, performance, and acceptability of each delivery method. The DSJI was the PharmaJet 2009 generation-1 device (G1) and the vaccine was measles-mumps-rubella vaccine from Bio-Manguinhos. Five hundred eighty-two healthy Brazilian infants were randomized to receive vaccine via G1 or NS. Seroconversion rates against measles and mumps viruses in the G1 treatment group did not meet non-inferiority criteria when compared with the NS group; however, responses in the G1 group to rubella virus were non-inferior to those of NS vaccinees. Most adverse events were mild or moderate. Crying after injection was more frequent in the NS group, and local skin reactions were more common in the G1 group. Five serious adverse events were judged causally unrelated to treatment and all resolved. Parents/guardians expressed a strong preference for G1 over NS for their children. Vaccinators found the G1 easy to use but noted incomplete vaccine delivery in some cases. Although the G1 has been superseded by an updated device, our results are important for the continued improvement and evaluation of DSJIs, which have the potential to overcome many of the challenges and risks associated with needle-based injections worldwide. Recommendations for future DSJI clinical studies include rigorous training of vaccinators, quantitative measurement of wetness on the skin following injection, and regular monitoring of device and vaccinator performance.

Putting respondent-driven sampling on the map: insights from Rio de Janeiro, Brazil.

BACKGROUND: Hard-to-reach populations with high background infection rates for HIV are particularly relevant in countries with restricted HIV epidemics, such as Brazil, where the very dynamics of the epidemic depends on the bridges between those populations and the general population. Respondent-driven sampling (RDS) has been one of the key strategies to assess such populations and inform policy making. OBJECTIVES: To geocode and visualize an RDS-based study on 605 heavy drug users, conducted in Rio de Janeiro, in 2009. METHODS: The location and characteristics of the residence of interviewees were collected by an Audio Computer-Assisted Self Interview (ACASI) survey, supplemented by additional information. Place of residence was geocoded and depicted as network graphs and thematic maps. RESULTS: The geographic distribution of the interviewees was found to be very heterogeneous. The recruiting chains progressed slowly during the successive waves toward neighborhoods far from the initial geographic axis. Despite the undeniable progress toward a broader geographic scope as the study proceeded through 11 successive waves, some key geographic areas were excluded. CONCLUSIONS: In the context of a large and complex urban area, plagued by structural violence and with a lively drug scene, the study made evident network bottlenecks. Either secondary to its relatively small sample size, structural constraints, or a combination of both, such bottlenecks represent a formidable challenge for RDS or other network-based methods as applied to urban settings with characteristics similar to Rio de Janeiro.

Reliability of self-report of HIV status among men who have sex with men in Brazil.

INTRODUCTION: The aim of this study was to evaluate the reliability of self-reported HIV among men who have sex with men (MSM) in Brazil. METHODS: MSM 18 years of age or older were recruited to a multicenter study using respondent-driven sampling. We compared self-report of the HIV test with a rapid HIV test using the kappa coefficient. RESULTS: A total of 3859 MSM were recruited, and 39% reported ever having an HIV test; their results were reported and they agreed to a new test. Agreement between self-report and the test was very good (kappa = 0.88). CONCLUSION: Our results suggest that self-report of HIV infection is a reliable indicator among MSM.

Antiretroviral drug resistance in a respondent-driven sample of HIV-infected men who have sex with men in Brazil.

BACKGROUND: : There are few studies on HIV subtypes and primary and secondary antiretroviral drug resistance (ADR) in community-recruited samples in Brazil. We analyzed HIV clade diversity and prevalence of mutations associated with ADR in men who have sex with men in all five regions of Brazil. METHODS: : Using respondent-driven sampling, we recruited 3515 men who have sex with men in nine cities: 299 (9.5%) were HIV-positive; 143 subjects had adequate genotyping and epidemiologic data. Forty-four (30.8%) subjects were antiretroviral therapy-experienced (AE) and 99 (69.2%) antiretroviral therapy-naïve (AN). We sequenced the reverse transcriptase and protease regions of the virus and analyzed them for drug resistant mutations using World Health Organization guidelines. RESULTS: : The most common subtypes were B (81.8%), C (7.7%), and recombinant forms (6.9%). The overall prevalence of primary ADR resistance was 21.4% (i.e. among the AN) and secondary ADR was 35.8% (i.e. among the AE). The prevalence of resistance to protease inhibitors was 3.9% (AN) and 4.4% (AE); to nucleoside reverse transcriptase inhibitors 15.0% (AN) and 31.0% (AE) and to nonnucleoside reverse transcriptase inhibitors 5.5% (AN) and 13.2% (AE). The most common resistance mutation for nucleoside reverse transcriptase inhibitors was 184V (17 cases) and for nonnucleoside reverse transcriptase inhibitors 103N (16 cases). CONCLUSIONS: : Our data suggest a high level of both primary and secondary ADR in men who have sex with men in Brazil. Additional studies are needed to identify the correlates and causes of antiretroviral therapy resistance to limit the development of resistance among those in care and the transmission of resistant strains in the wider epidemic.

Avaliação da técnica de amostragem respondent-driven sampling na estimação de prevalências de doenças transmissíveis em populações organizadas em redes complexas / Evaluation of sampling respondent-driven sampling in the estimation of prevalence of diseases in populations organized in complex networks

Diversos fatores podem dificultar a caracterização acurada do perfil de umapopulação por amostragem. Se a característica que define a população é de difícil observação – seja porque exige testes caros para detecção ou porque é uma característica de comportamento ilegal ou estigmatizado que dificulta a identificação, torna-se praticamente impossível aplicar os métodos clássicos de amostragem, poisnão se pode definir uma base de amostragem (sampling frame). Populações desse tipo são conhecidas como populações ocultas, ou escondidas, e alguns exemplos comumente estudados são homens que fazem sexo com homens, trabalhadores do sexo e usuários de drogas. Essa dissertação discute a técnica de amostragemconhecida como Respondent-Driven Sampling (RDS), originalmente proposta por Heckathorn (1997), e que vem sendo amplamente utilizada na estimação de prevalências de doenças transmissíveis em populações ocultas. Esse método pertence à família de amostragens por bola-de-neve, na qual os elementos seguintes da amostra são recrutados a partir da rede de conhecidos dos elementos já presentesna amostra, formando as cadeias de referência. Com este método, além dasinformações individuais, é possível estudar também as relações entre os indivíduos. O recrutamento por bola de neve não gera uma amostra aleatória, e está sujeito às propriedades das redes sociais das populações em estudo, que deve mudar de lugar para lugar e potencialmente influenciar as medidas de prevalência geradas. As redes sociais são estruturas complexas, e compreender como que a amostragemRDS é influenciada por estas estruturas é um dos objetivos dessa dissertação. Além disso, se o interesse de um estudo epidemiológico é estimar a prevalência de uma doença transmissível, há de se considerar que muitas vezes a própria rede social pode estar correlacionada com as redes de transmissão, gerando potenciais dependências entre o processo de amostragem e a distribuição da variável desfecho...

Intervenção farmacêutica e prevenção de eventos adversos / Pharmaceutical intervention and prevention of drug related problems

No presente estudo, são relatadas as intervenções realizadas pelo serviço de farmácia junto ao corpo clínico de uma instituição pública federal, referência nacional para cirurgias de alta complexidade em ortopedia no Rio de Janeiro. Realizou-se estudo retrospectivo no qual foram analisadas as intervenções farmacêuticas realizadas entre junho de 2004 e junho de 2005. O serviço de farmácia atendeu 13,6% dos 5476 pacientes internados neste período. Dos pacientes atendidos, 30,4% necessitaram de pelo menos uma intervenção deste profissional junto ao corpo clínico em algum momento da sua internação, perfazendo um total de 227 intervenções. Os médicos foram os profissionais mais contatados (71,1%), seguidos dos enfermeiros (16,9%) e auxiliares de enfermagem (4,6%). Dos problemas detectados, 84,1% correspondiam a erros, dos quais 49,5% foram prevenidos com as intervenções. A análise dos erros encontrados nos permite sugerir alguns dos principais problemas relacionados a medicamentos apresentados pelos pacientes da instituição. Das intervenções realizadas, 70% foram aceitas, sendo este percentual de 60% para as intervenções relacionadas à prescrição. Os resultados sugerem que as intervenções farmacêuticas foram ferramentas efetivas para a prevenção de eventos adversos, reforçando a importância da assistência farmacêutica para a qualidade da assistência hospitalar.

In the present study, we describe the pharmaceutical interventions performed by the pharmacy service of a publicorthopaedic hospital at Rio de Janeiro, Brazil. In a retrospective study, we analysed the pharmaceutical interventions performed during a year (from june 2004 to june 2005). The pharmacy service assisted 13.6% of the5476 patients that were submitted to internation. In 30.4 % of the patients that were directly assisted by the pharmacist was identified the necessity of pharmaceutical interventions, reaching 227 interventions during the period of the study. The physicians were the most requested professionals (71.1%), followed by nurses 16.9%. Eighty four percent of the problems that were detected were related to potential medication errors. Forty nine percent of these errors were prevented by the pharmacists. It was possible to predict some of the potential drug related problems that could be related to these patients as well. Seventy percent of the pharmaceutical interventions were accepted by the professionals. For the interventions related to prescription,sixty percent were accepted. The results suggest that pharmaceutical interventions were effective to prevent drug adverse events, reinforcing the important role of pharmacists in hospital assistance.

Purification and characterization of a beta-glucuronidase present during embryogenesis of the mollusk Pomacea sp.

A beta-glucuronidase was purified from Pomacea sp. eggs by ammonium sulfate fractionation, DEAE-BioGel and Heparin-Sepharose chromatographies. This enzyme showed a Mr 180 kDa, with subunits of 90 kDa. The kinetic parameters were: pH 4.0, temperature 60 degrees C, Km 2.7 x 10(-6) and Vmax 15.3 microM/h, activator Mg+2, and inhibitor: lactone of D-saccharic acid. beta-glucuronidase is an exoglucuronidase involved in glycosaminoglycans metabolism with kinetics parameters similar to those found in mammals.