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The reported frequency and types of adverse events following initial vaccination and revaccination with Bacille Calmette-Guérin (BCG) varies worldwide. Using active surveillance in a randomised controlled trial of BCG vaccination (the BRACE trial), we determined the incidence and risk factors for the development of BCG injection site abscess and re...
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Context 1
... median diameter was 2.0 cm (IQR 2.0-2.5) (Fig. 3). All abscesses, except for one, were discharged (most commonly 'yellow cloudy' fluid) and 24/41 (59%) had persistent discharge for more than 2 weeks. All participants, except for one, experienced pain or tenderness at the abscess site. One participant with a 5.0 cm abscess presented to an emergency department with severe injection ...
Citations
... Further review in prospective research is necessary to fully assess the results; however, they are beneficial for idea formulation. There is a lack of information about possible confounding factors, including dietary habits, socioeconomic status, and TB exposure status [44]. After 15 years of follow-up after immunization, the prior research found that BCG revaccination provides 36% protection against TB. ...
Bacillus Calmette-Guérin (BCG) vaccination remains a cornerstone in global efforts to combat tuberculosis (TB), a persistent public health threat worldwide. The purpose of this systematic review is to find out how well BCG revaccination protects against TB. This systematic review synthesized recent studies investigating the efficacy of BCG vaccination in preventing TB infection and disease. A total of 15 relevant publications were identified through a comprehensive search across multiple databases, including Cochrane Library, PubMed, Medline, and Scopus. The inclusion criteria encompassed studies involving humans, written in English, and categorized as case-control, cohort, meta-analysis, or full-text. Studies were selected based on their relevance to BCG revaccination and protection against TB, and a standardized data extraction form was used to gather pertinent information from each study. Quality assessment was conducted using established tools to evaluate the rigor, study design, and risk of bias in each included study. The findings revealed significant insights into BCG's effectiveness across different populations and age groups. Several studies demonstrated a substantial reduction in latent TB infection (LTBI) and incidence rates of TB following BCG vaccination. However, the protective efficacy of BCG revaccination varied across studies and populations, with some indicating modest protection against TB disease development, particularly in high-risk populations like healthcare workers. Furthermore, investigations into the immunological mechanisms underlying BCG's protective efficacy provided valuable insights into cytokine/chemokine profiles and immunomodulatory properties.
... In studies on bladder cancer patients no preliminary testing for anti-Mycobacterium immunity was performed, and it would be of great interest to determine whether tuberculin status influences both bladder cancer remission and later dementia protection in recipients of intravesicular BCG. Centrally, concerns about pre-existing mycobacterial immunity may be unfounded because repeat administration of BCG appeared to have no ill effects, as suggested by several repeat inoculation studies (e.g., [52,82,83]). ...
... However, adults are the target population in the context of dementia prevention. In studies on individuals aged 19-74 years, abscess and/or lymphadenopathy was seen in ~3% of vaccine recipients, that generally resolved upon treatment [82,83]. Nevertheless, given suggestions that elderly individuals, particularly those at risk of AD, may have some degree of immune decline [2], close monitoring of vaccine recipients is warranted. ...
There is growing awareness that infections may contribute to the development of senile dementia including Alzheimer’s disease (AD), and that immunopotentiation is therefore a legitimate target in the management of diseases of the elderly including AD. In Part I of this work, we provided a historical and molecular background to how vaccines, adjuvants, and their component molecules can elicit broad-spectrum protective effects against diverse agents, culminating in the development of the tuberculosis vaccine strain Bacille Calmette–Guérin (BCG) as a treatment for some types of cancer as well as a prophylactic against infections of the elderly such as pneumonia. In Part II, we critically review studies that BCG and other vaccines may offer a measure of protection against dementia development. Five studies to date have determined that intravesicular BCG administration, the standard of care for bladder cancer, is followed by a mean ∼45% reduction in subsequent AD development in these patients. Although this could potentially be ascribed to confounding factors, the finding that other routine vaccines such as against shingles (herpes zoster virus) and influenza (influenza A virus), among others, also offer a degree of protection against AD (mean 29% over multiple studies) underlines the plausibility that the protective effects are real. We highlight clinical trials that are planned or underway and discuss whether BCG could be replaced by key components of the mycobacterial cell wall such as muramyl dipeptide. We conclude that BCG and similar agents merit far wider consideration as prophylactic agents against dementia.
... 12,17 To consider BCG revaccination, we must acknowledge that the rate of adverse events (AE) also varies globally. While BCG vaccine batch variability was found by Soh and colleagues (2014) to affect the occurrence of AEs, 18 Villanueva et al. 19 did not find any association between the BCG vaccine batch and AEs. There is thus a paucity of evidence comparing the effectiveness and safety of different BCG batches. ...
... 3 This finding is recalled in this issue (see below). Villanueva et al. 19 reported an increased risk of injection site abscess and lymphadenopathy following BCG revaccination in Australian health care workers (HCW) during the influenza vaccination campaign. ...
... Severe AEs were very few and limited to subcutaneous abscesses and lymphadenitis. This is in striking contrast to the earlier findings by Villanueva et al. 19 In the current issue, Sánchez-García and colleagues 21 concluded that BCG revaccination in a previously immunized Mexican population was safe. ...
... Similar to our observations, they observed erythema in 87% of the participants, and lymphadenopathy in 3% of the subjects. 18 Rho et al. determined that the incidence of adverse events per 100,000 BCG doses was found to be 41.6 for intradermal Danish strains and 25.9 for 100,000 intradermal Tokyo strains. 19 These previous observations may support our findings. ...
The bacille Calmette-Guérin (BCG) vaccine is administered in many countries as part of their vaccination schedules. Epidemiologic studies have suggested a possible benefit of this vaccine in the context of the COVID-19 pandemic and other respiratory infections. We aimed to assess the safety of this intervention in BCG-primed adults. Adult health care workers (n = 451) received a single intradermal application of the BCG vaccine (Tokyo 172 strain) in the deltoid region of the right arm. Follow-up (30 days) calls and clinical inspections were guided using a standardized data sheet to assess local and systemic reactions. Early local reactions were common at 24 h and 7 days, such as erythema (74.9%, 69.2%), induration (55.7%, 59%), a papule (53.4%, 47.7%), and edema (48.3%, 38.1). Local symptoms (pruritus 44.8%, heat 16.2%, and pain 34.8%) were less frequent at day 7. Late expected reactions (14 and 30 days) included the formation of crusts (39.6% and 63.9%), a pustule (36.6% and 17%), or ulcers (28.8% and 17.7%). Severe reactions were limited to subcutaneous abscesses (2%) and lymphadenitis (<1%).
... 9 We previously reported that BCG revaccination in Australian participants who were randomized within 3 days of influenza vaccination was associated with more frequent injection site abscess and regional lymphadenopathy. 10 In this report, we evaluate the overall incidence of local adverse events and serious adverse events in the BRACE trial, as well as the impact of revaccination on local injection site reactions. ...
... Revaccination has been associated with an increased risk of common local injection site reactions, as well as adverse events, such as injection site abscess and lymphadenopathy. 10,30 In this study, which included participants from five countries, we found that a higher proportion of participants in the BCGrevaccinated group experienced the common local injection site reactions of pain, erythema, swelling, or itch, compared with the BCG-naïve group. Interestingly, injection site erythema and swelling occurred earlier and were of shorter duration in the Data are presented as n (%) or median (interquartile range), unless otherwise specified. ...
... 2,30,37,38,43 Diverse definitions exist in the literature, with a variety of surveillance methods, and using different BCG strains. 10 We used a broad definition with active surveillance and a higher (adult) BCG dose compared with studies in children. 15 Moreover, 0.5% of the placebo group reported regional lymphadenopathy, with a similar time to onset, resolution and size to those who received BCG, highlighting that regional lymphadenopathy following vaccination may not always be related to the vaccine itself. ...
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.
... In 2022, an article published in the journal npj Vaccines investigated the incidence and risk factors for the development of BCG injection-site abscesses and local lymphadenopathy. Results showed that 3% of 1387 BCG-vaccinated participants developed injection-site abscesses, with the majority (34/41, 83%) resolving without treatment [136]. Furthermore, the incidence of injection-site abscesses was higher in participants who received BCG revaccination (OR 3.6, 95% CI 1.7-7.5) ...
... Furthermore, the incidence of injection-site abscesses was higher in participants who received BCG revaccination (OR 3.6, 95% CI 1.7-7.5) [136]. Additionally, local lymph node lesions were observed in 48 out of 1387 (3%) participants who received the BCG vaccine. ...
... Interestingly, a higher incidence of these lesions was found among individuals who underwent BCG revaccination (odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-3.9) [136]. It is worth noting that the frequency and types of adverse events associated with initial BCG vaccination and revaccination vary across different geographical regions. ...
Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a prevalent global infectious disease and a leading cause of mortality worldwide. Currently, the only available vaccine for TB prevention is Bacillus Calmette–Guérin (BCG). However, BCG demonstrates limited efficacy, particularly in adults. Efforts to develop effective TB vaccines have been ongoing for nearly a century. In this review, we have examined the current obstacles in TB vaccine research and emphasized the significance of understanding the interaction mechanism between MTB and hosts in order to provide new avenues for research and establish a solid foundation for the development of novel vaccines. We have also assessed various TB vaccine candidates, including inactivated vaccines, attenuated live vaccines, subunit vaccines, viral vector vaccines, DNA vaccines, and the emerging mRNA vaccines as well as virus-like particle (VLP)-based vaccines, which are currently in preclinical stages or clinical trials. Furthermore, we have discussed the challenges and opportunities associated with developing different types of TB vaccines and outlined future directions for TB vaccine research, aiming to expedite the development of effective vaccines. This comprehensive review offers a summary of the progress made in the field of novel TB vaccines.
... There was no serious AE reported in our trial and the already known local reactions after BCG administration occurred in the intensity expected, even though they occurred earlier than what is described in newborns, similar to the BATTLE trial [28] . On the contrary, Villanueva et al. [29] , reported an increased risk of injection site abscess or lymphadenopathy after the BCG Danish strain revaccination during the BRACE trial, which was also conducted to study the effect of BCG on COVID-19 but with no results published yet. ...
Introduction:
Bacillus Calmette-Guérin (BCG) vaccine was considered as a tool against SARS-CoV-2 based on the concept of trained immunity, which could be useful against emerging pathogens.
Methods:
A multicenter double-blinded randomized clinical trial recruited health care workers (HCW) in Brazil. The incidence rates of COVID-19, clinical manifestations, absenteeism, and adverse events among HCW receiving BCG vaccine (Moreau or Moscow strains) or placebo were compared. BCG vaccine-mediated immune response before and after implementing specific vaccines for COVID-19 (CoronaVac® or CovishieldTM) was analyzed. Cox proportional hazard and linear mixed effect modelling were used.
Results:
264 volunteers were included for analysis (BCG=134 and placebo=130). Placebo group presented a COVID-19 cumulative incidence of 0.75% versus 0.52% of BCG. Moreau strain also presented a higher incidence rate (1.60% x 0.22%). BCG did not show a protective hazard ratio against COVID-19. In addition, the log(IgG) level against SARS-CoV-2 presented a higher increase in the BCG group, whether or not participants had COVID-19, but also without statistical significance.
Conclusion:
Our results suggest a BCG's tendency of protection against SARS-CoV-2 and higher IgG levels when compared to placebo. The clinical trial was registered at https://clinicaltrials.gov/ (NCT04659941).
... BCG has inherent advantages over the new vaccine candidates since it has been used over many decades, and the health system is optimized for vaccine administration. A systematic review on the safety of BCG revaccination concluded that there was minimal risk 21 , while a study from Australia among adults observed an increased risk of abscess and lymphadenopathy among the revaccinated, which resolved within a month without intervention 22 . In this context, detailed documentation of adverse events following immunization in those with prior BCG vaccination is essential. ...
Background & objectives:
Vaccines play a crucial role in the prevention of tuberculosis (TB). Revaccination with Bacille Calmette-Guerin (BCG) for the prevention of TB is an important strategy that is currently gaining interest. The objective of this study was to reanalyze the community-based Chingleput BCG vaccination trial for protective efficacy of BCG revaccination against incident TB disease.
Methods:
A retrospective analysis of the Chingleput BCG vaccination trial (conducted in 1968) data was carried out. Data on participants with evidence of prior BCG vaccination at trial intake and randomized to BCG vaccine [low dose (0.01 mg), high dose (0.1 mg)] and placebo arms were analyzed. The incidence of TB disease, which was based on sputum culture and/or chest X-ray was compared between the BCG and placebo arms over a 15 yr follow up period.
Results:
Of the 269,727 individuals randomized in the trial; 263,158 had no evidence of TB at baseline, of which 4436 (1.68%) had evidence of BCG vaccination at trial intake (2890 in the BCG vaccine and 1546 in the placebo arms, respectively). There were 77 (190 per 100,000) and 64 (296 per 100,000) incident TB cases in the BCG and placebo arm, respectively, at 15 yr post-vaccination. The incidence of TB disease was significantly lower in the BCG arm [Hazard ratio of BCG arm (95% confidence interval): 0.64 (0.46-0.89)].
Interpretation & conclusions:
Retrospective data analysis of this community-based trial revealed that BCG revaccination in a community offered modest protection against the development of TB disease at the end of 15 years which, however, requires further evaluation.
Nearly one‐fourth of the global population is infected by Mycobacterium tuberculosis ( Mtb ), and approximately 90%–95% remain asymptomatic as latent tuberculosis infection (LTBI), an estimated 5%–10% of those with latent infections will eventually progress to active tuberculosis (ATB). Although it is widely accepted that LTBI transitioning to ATB results from a disruption of host immune balance and a weakening of protective immune responses, the exact underlying immunological mechanisms that promote this conversion are not well characterized. Thus, it is difficult to accurately predict tuberculosis (TB) progression in advance, leaving the LTBI population as a significant threat to TB prevention and control. This article systematically explores three aspects related to the immunoregulatory mechanisms and translational research about LTBI: (1) the distinct immunocytological characteristics of LTBI and ATB, (2) LTBI diagnostic markers discovery related to host anti‐TB immunity and metabolic pathways, and (3) vaccine development focus on LTBI.
This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology
Infectious Diseases > Genetics/Genomics/Epigenetics
Immune System Diseases > Genetics/Genomics/Epigenetics
