Safety of BCG vaccination and revaccination in healthcare workers.

BCG vaccination and revaccination are increasingly being considered for the protection of adolescents and adults against tuberculosis and, more broadly, for the off-target protective immunological effects against other infectious and noninfectious diseases. Within an international randomized controlled trial of BCG vaccination in healthcare workers (the BRACE trial), we evaluated the incidence of local and serious adverse events, as well as the impact of previous BCG vaccination on local injection site reactions (BCG revaccination). Prospectively collected data from 99% (5351/5393) of participants in Australia, Brazil, Spain, The Netherlands and the UK was available for analysis. Most BCG recipients experienced the expected self-limiting local injection site reactions (pain, tenderness, erythema, swelling). BCG injection site itch was an additional common initial local symptom reported in 49% of BCG recipients. Compared to BCG vaccination in BCG-naïve individuals, BCG revaccination was associated with increased frequency of mild injection site reactions, as well as earlier onset and shorter duration of erythema and swelling, which were generally self-limiting. Injection site abscess and regional lymphadenopathy were the most common adverse events and had a benign course. Self-resolution occurred within a month in 80% of abscess cases and 100% of lymphadenopathy cases. At a time when BCG is being increasingly considered for its off-target effects, our findings indicate that BCG vaccination and revaccination have an acceptable safety profile in adults.

Factors influencing scar formation following Bacille Calmette-Guérin (BCG) vaccination.

The prevalence of scar formation following Bacille Calmette-Guérin (BCG) vaccination varies globally. The beneficial off-target effects of BCG are proposed to be stronger amongst children who develop a BCG scar. Within an international randomised trial ('BCG vaccination to reduce the impact of coronavirus disease 2019 (COVID-19) in healthcare workers'; BRACE Trial), this nested prospective cohort study assessed the prevalence of and factors influencing scar formation, as well as participant perception of BCG scarring 12 months following vaccination . Amongst 3071 BCG-recipients, 2341 (76%) developed a BCG scar. Scar prevalence was lowest in Spain and highest in UK. Absence of post-injection wheal (OR 0.4, 95%CI 0.2-0.9), BCG revaccination (OR 1.7, 95%CI 1.3-2.0), female sex (OR 2.0, 95%CI 1.7-2.4), older age (OR 0.4, 95%CI 0.4-0.5) and study country (Brazil OR 1.6, 95%CI 1.3-2.0) influenced BCG scar prevalence. Of the 2341 participants with a BCG scar, 1806 (77%) did not mind having the scar. Participants more likely to not mind were those in Brazil, males and those with a prior BCG vaccination history. The majority (96%) did not regret having the vaccine. Both vaccination-related (amenable to optimisation) and individual-related factors affected BCG scar prevalence 12 months following BCG vaccination of adults, with implications for maximising the effectiveness of BCG vaccination.

Erratum: Factors influencing scar formation following Bacille Calmette-Guérin (BCG) vaccination.

[This corrects the article DOI: 10.1016/j.heliyon.2023.e15241.].

Fatores associados ao tempo para realização do transplante renal pediátrico com doador falecido a partir da inscrição na lista de espera no estado do Rio de Janeiro / Factors associated with time to deceased donor pediatric kidney transplant for waitlisted children in Rio de Janeiro state

O transplante renal é a terapia de substituição renal com melhor sobrevida e qualidade de vida para crianças e adolescentes com falência de rins. O transplante de rins com doador falecido é a modalidade de transplante mais comumente realizada no Brasil e em muitos países. Este trabalho teve o objetivo de avaliar os fatores relacionados ao tempo até o primeiro transplante renal com doador falecido em crianças e adolescentes até 18 anos de idade a partir da inscrição na fila de espera para transplante renal. Foi realizado estudo retrospectivo com dados de crianças e adolescentes inscritas no cadastro técnico único (CTU) do sistema nacional de transplantes (SNT) referentes ao estado do Rio de Janeiro no período de 01/01/2012 a 30/06/2022. Foram realizadas análise de sobrevivência com eventos competitivos (transplante renal com doador vivo, remoção da lista e óbito) e regressão semiparamétrica de Cox. O estudo teve uma amostra de 296 crianças e adolescentes inscritos na lista de transplante renal, dos quais 75,6% transplantaram com doador falecido com tempo mediano de 112 dias. A maioria das crianças e adolescentes inscrita tinha entre 7 e 18 anos de idade (90%), era do sexo masculino (56%) e da raça/cor branca (45,6%), com PRA menor que 50% (96,6%), tipagem sanguínea A ou O (845), já havia transfundido (65,5%) e iniciado diálise antes de serem listados (86,1%). Um terço dos inscritos apresentava glomerulonefrite como doença de base. Na análise univariada, estar vinculado a centro transplantador com baixo volume de transplantes (HR 0,26 / IC 0,17-0,39), PRA ≥50% (HR 0,27 / IC 0,09-0,85) e idade entre 7 e 18 anos (HR 0,51 / IC 0,33-0,79) impactaram negativamente o tempo até o transplante renal com doador falecido. Ao passo que estar inscrito na época da pandemia de COVID-19 (HR 74 / IC 10,4-525) aumentou a probabilidade de transplantar com doador falecido. Já na análise múltipla, a oferta de rins (HR 1,01 / IC 1,003-1,03) e ter insuficiência renal crônica (HR 1,52 / IC 1,07-2,14) tiveram impacto positivo na probabilidade de receber transplante renal com doador falecido, enquanto PRA ≥50% (HR 0,17 / IC 0,05-0,56) e estar vinculado a centro de baixo volume (HR 0,67 / IC 0,45- 0,99) tiveram efeito negativo. Não se mostrou diferença em relação ao acesso ao transplante renal com doador falecido a partir da inscrição na fila de espera no que diz respeito a sexo, raça/cor, status socioeconômico, distância de moradia até o centro transplantador, tipagem sanguínea ou transfusão de sangue. Este estudo mostrou que o fator imunológico (PRA) e a característica do centro transplantador mostraram ser as únicas variáveis que impactaram o tempo até o transplante renal pediátrico com doador falecido mesmo quando controladas pelo efeito das outras variáveis.

Kidney transplantation offers better survival and quality of life than any other modality of kidney replacement therapy for children and teenagers with kidney failure. Deceased donor kidney transplant (DDKT) is the most frequent type of kidney transplant in Brazil and many countries. This work aims to evaluate the factors related to time until first DDKT in waitlisted children and teenagers up to 18 years old. In this retrospective study, data for kidney transplant waitlisted patients under 19 years old in Rio de Janeiro state was collected from the national transplant system of the Ministry of Health, from January 1 st , 2012, to June 30th , 2022. Survival analysis was performed with time to first DDKT as the outcome. Cox proportional hazards regression models with competing risks were also employed. Of the 296 waitlisted patients, 75,6% had DDKT with a median time of 112 days. Most of the waitlisted patients were between 7 and 18 years old (90%), male (56%) and white (45,6%). The majority had PRA of less than 50% (96,6%), blood type A or O (84%), had received blood transfusion (65,5%) and were on kidney replacement therapy (86,1%) before entering the waitlist. Glomerulonephritis was the cause of kidney disease in one third of the cases. In the univariate analysis, being listed by a low volume transplanting center (HR 0,26 / CI 0,17-0,39), PRA ≥50% (HR 0,27 / CI 0,09-0,85) and age between 7 and 18 years old (HR 0,51 / CI 0,33-0,79) had a negative impact on waitlist time to DDKT. Meanwhile, being listed during the COVID-19 pandemic (HR 74 / CI 10,4-525) increased the likelihood of undergoing a DDKT. Multivariable analysis confirmed the negative impact of PRA ≥50% % (HR 0,17 / CI 0,05-0,56) and being listed by a low volume transplanting center (HR 0,67 / CI 0,45-0,99) at the time of DDKT. On the hand, it was shown that the number of deceased donor kidneys (HR 1,01 / CI 1,003-1,03) and chronic kidney disease as cause of kidney failure (HR 1,52 / CI 1,07-2,14) increased the chance of DDKT. This work didn't show any difference in access to DDKT for waitlisted patients under 19 years old in terms of sex, race/skin color, socioeconomic status, distance between residence and transplanting center, blood type or blood transfusion. Finally, by accounting for clinical individual patient features and external factors, this study concluded that immunological status (PRA) and low volume transplanting centers were the only variables that impacted time to DDKT, even after controlling for covariables.