Vanessa dos Reis von Doellinger

Duration of post-vaccination immunity against yellow fever in adults

INTRODUCTION Available scientific evidence to recommend or to advise against booster doses of yellow fever vaccine (YFV) is inconclusive. A study to estimate the seropositivity rate and geometric mean titres (GMT) of adults with varied times of vaccination was aimed to provide elements to revise the need and the timing of revaccination. METHODS Adults from the cities of Rio de Janeiro and Alfenas located in non-endemic areas in the Southeast of Brazil, who had one dose of YFV, were tested for YF neutralising antibodies and dengue IgG. Time (in years) since vaccination was based on immunisation cards and other reliable records. RESULTS From 2011 to 2012 we recruited 691 subjects (73% males), aged 18-83 years. Time since vaccination ranged from 30 days to 18 years. Seropositivity rates (95%C.I.) and GMT (International Units/mL; 95%C.I.) decreased with time since vaccination: 93% (88-96%), 8.8 (7.0-10.9) IU/mL for newly vaccinated; 94% (88-97), 3.0 (2.5-3.6) IU/mL after 1-4 years; 83% (74-90), 2.2 (1.7-2.8) IU/mL after 5-9 years; 76% (68-83), 1.7 (1.4-2.0) IU/mL after 10-11 years; and 85% (80-90), 2.1 (1.7-2.5) IU/mL after 12 years or more. YF seropositivity rates were not affected by previous dengue infection. CONCLUSIONS Eventhough serological correlates of protection for yellow fever are unknown, seronegativity in vaccinated subjects may indicate primary immunisation failure, or waning of immunity to levels below the protection threshold. Immunogenicity of YFV under routine conditions of immunisation services is likely to be lower than in controlled studies. Moreover, infants and toddlers, who comprise the main target group in YF endemic regions, and populations with high HIV infection rates, respond to YFV with lower antibody levels. In those settings one booster dose, preferably sooner than currently recommended, seems to be necessary to ensure longer protection for all vaccinees.

Booster dose after 10 years is recommended following 17DD-YF primary vaccination

A single vaccination of Yellow Fever vaccines is believed to confer life-long protection. In this study, results of vaccinees who received a single dose of 17DD-YF immunization followed over 10 y challenge this premise. YF-neutralizing antibodies, subsets of memory T and B cells as well as cytokine-producing lymphocytes were evaluated in groups of adults before (NVday0) and after (PVday30-45, PVyear1-4, PVyear5-9, PVyear10-11, PVyear12-13) 17DD-YF primary vaccination. YF-neutralizing antibodies decrease significantly from PVyear1-4 to PVyear12-13 as compared to PVday30-45, and the seropositivity rates (PRNT≥2.9Log10mIU/mL) become critical (lower than 90%) beyond PVyear5-9. YF-specific memory phenotypes (effector T-cells and classical B-cells) significantly increase at PVday30-45 as compared to naïve baseline. Moreover, these phenotypes tend to decrease at PVyear10-11 as compared to PVday30-45. Decreasing levels of TNF-α+ and IFN-γ+ produced by CD4+ and CD8+ T-cells along with increasing levels of IL-10+CD4+T-cells were characteristic of anti-YF response over time. Systems biology profiling represented by hierarchic networks revealed that while the naïve baseline is characterized by independent micro-nets, primary vaccinees displayed an imbricate network with essential role of central and effector CD8+ memory T-cell responses. Any putative limitations of this cross-sectional study will certainly be answered by the ongoing longitudinal population-based investigation. Overall, our data support the current Brazilian national immunization policy guidelines that recommend one booster dose 10 y after primary 17DD-YF vaccination.

Adverse events following yellow fever immunization: Report and analysis of 67 neurological cases in Brazil

Neurological adverse events following administration of the 17DD substrain of yellow fever vaccine (YEL-AND) in the Brazilian population are described and analyzed. Based on information obtained from the National Immunization Program through passive surveillance or intensified passive surveillance, from 2007 to 2012, descriptive analysis, national and regional rates of YFV associated neurotropic, neurological autoimmune disease, and reporting rate ratios with their respective 95% confidence intervals were calculated for first time vaccinees stratified on age and year. Sixty-seven neurological cases were found, with the highest rate of neurological adverse events in the age group from 5 to 9 years (2.66 per 100,000 vaccine doses in Rio Grande do Sul state, and 0.83 per 100,000 doses in national analysis). Two cases had a combination of neurotropic and autoimmune features. This is the largest sample of YEL-AND already analyzed. Rates are similar to other recent studies, but on this study the age group from 5 to 9 years of age had the highest risk. As neurological adverse events have in general a good prognosis, they should not contraindicate the use of yellow fever vaccine in face of risk of infection by yellow fever virus.

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.

Morbidity and mortality associated with injuries: results of the Global Burden of Disease study in Brazil, 2008

The aim of this study was to estimate the global burden of disease from external causes in 2008 in Brazil, based on DALYs (disability-adjusted life years). YLLs (years of life lost) were estimated according to the method proposed by Murray & Lopez (1996). Meanwhile, the method for estimating YLDs (years lived with disability) included methodological adjustments taking the Brazilian reality into account. The study showed a total of 195 DALYs per 100 thousand inhabitants, of which 19 DALYs were related to external causes. Among YLLs, 48% were from unintentional causes and 52% from intentional causes. Among YLDs, unintentional causes predominated, with 95%. The share of YLLs in DALYs was 90%. The cause with the highest proportion of YLLs was “homicide and violence” (43%), followed by “road traffic accidents” (31%). Falls accounted for the highest share of YLDs (36%). The sex ratio (male-to-female) was 4.8 for DALYs, and the predominant age bracket was 15-29 years. Since external causes are avoidable, the study provides potentially useful information for policymakers in public security and health.

Diferenciais de morbimortalidade por causas externas: resultados do estudo carga global de doenças no Brasil, 2008

The aim of this study was to estimate the global burden of disease from external causes in 2008 in Brazil, based on DALYs (disability-adjusted life years). YLLs (years of life lost) were estimated according to the method proposed by Murray & Lopez (1996). Meanwhile, the method for estimating YLDs (years lived with disability) included methodological adjustments taking the Brazilian reality into account. The study showed a total of 195 DALYs per 100 thousand inhabitants, of which 19 DALYs were related to external causes. Among YLLs, 48% were from unintentional causes and 52% from intentional causes. Among YLDs, unintentional causes predominated, with 95%. The share of YLLs in DALYs was 90%. The cause with the highest proportion of YLLs was “homicide and violence” (43%), followed by “road traffic accidents” (31%). Falls accounted for the highest share of YLDs (36%). The sex ratio (male-to-female) was 4.8 for DALYs, and the predominant age bracket was 15-29 years. Since external causes are avoidable, the study provides potentially useful information for policymakers in public security and health.

Immune response to the mumps component of the MMR vaccine in the routine of immunisation services in the Brazilian National Immunisation Program

A non-controlled longitudinal study was conducted to evaluate the combined vaccine against measles, mumps and rubella (MMR) immunogenicity in 150 children vaccinated in the routine of three health units in the city of Rio de Janeiro, Brazil, 2008-2009, without other vaccines administered during the period from 30 days before to 30 days after vaccination. A previous study conducted in Brazil in 2007, in 1,769 children ranging from 12-15 months of age vaccinated against yellow fever and MMR simultaneously or at intervals of 30 days or more between doses, had shown low seroconversion for mumps regardless of the interval between administration of the two vaccines. The current study showed 89.5% (95% confidence interval: 83.3; 94.0) seroconversion rate for mumps. All children seroconverted for measles and rubella. After revaccination, high antibody titres and seroconversion rates were achieved against mumps. The results of this study and others suggest that two MMR doses confer optimal immunoresponses for all three antigens and the possible need for additional doses should be studied taking into account not only serological, but also epidemiological data, as there is no serological correlate of protection for mumps.

Morbimortalidad por las causas externas: resultados del estudio Carga Global de las Enfermedades en Brasil, 2008

The aim of this study was to estimate the global burden of disease from external causes in 2008 in Brazil, based on DALYs (disability-adjusted life years). YLLs (years of life lost) were estimated according to the method proposed by Murray & Lopez (1996). Meanwhile, the method for estimating YLDs (years lived with disability) included methodological adjustments taking the Brazilian reality into account. The study showed a total of 195 DALYs per 100 thousand inhabitants, of which 19 DALYs were related to external causes. Among YLLs, 48% were from unintentional causes and 52% from intentional causes. Among YLDs, unintentional causes predominated, with 95%. The share of YLLs in DALYs was 90%. The cause with the highest proportion of YLLs was “homicide and violence” (43%), followed by “road traffic accidents” (31%). Falls accounted for the highest share of YLDs (36%). The sex ratio (male-to-female) was 4.8 for DALYs, and the predominant age bracket was 15-29 years. Since external causes are avoidable, the study provides potentially useful information for policymakers in public security and health.