Moderna COVID-19 vaccine was linked to myocarditis or myopericarditis at 28 d (4.2 events/100 000 persons).

SOURCE CITATION: Husby A, Hansen JV, Fosbøl E, et al. SARS-CoV-2 vaccination and myocarditis or myopericarditis: population based cohort study. BMJ. 2021;375:e068665. 34916207.

Spectrum of Inborn errors of immunity in a cohort of 90 patients presenting with complications to BCG vaccination in India.

World Health Organisation recommends the practice of BCG vaccination at birth in countries which have a high incidence of tuberculosis and/or high leprosy burden. The BCG vaccination is considered safe for a competent immune system. However, in children with weakened immune systems cause of which can be primary or secondary, the vaccine may lead to side effects which can be localized or disseminated. In this study, we report a spectrum of inborn errors of immunity (IEI) commonly referred to as primary immunodeficiency disorders (PIDs) diagnosed in a large cohort of patients presenting with complications to BCG vaccination from India. Retrospective data analysis of patients referred to ICMR- National Institute of Immunohematology (ICMR-NIIH) for IEI workup between 2007 and 2019 was done. IEI was identified in n = 52/90 (57.7%) patients presenting with BCG complications. Of these, n = 13(14.4%) patients were diagnosed with severe combined immune deficiency, n = 15(16.7%) with chronic granulomatous disease, n = 19(21.1%) with Inborn errors of IFN-γ immunity, n = 4(4.4%) with Combined immunodeficiency and n = 1(1.1%) with Leucocyte Adhesion Deficiency type1. Majority of cases with BCGosis (88%) had an underlying IEI. This study strongly highlights the need for evaluation of patients with BCG complications for underlying IEI. While disseminated BCGosis strongly predicts underlying IEI, even localized persistent adenitis may be a warning sign of underlying IEI. It is also strongly recommended to record a family history of previous sibling death prior to administration of this live vaccine and deferring live vaccine till the diagnosis of IEI is ruled out in cases with a positive family history.

BCG and Adverse Events in the Context of Leprosy.

Background: Notwithstanding its beneficial immunoprophylactic outcomes regarding leprosy and childhood TB, BCG vaccination may cause adverse events, particularly of the skin. However, this local hyper-immune reactivity cannot be predicted before vaccination, nor is its association with protection against leprosy known. In this study we investigated the occurrence of adverse events after BCG (re)vaccination in contacts of leprosy patients and analyzed whether the concomitant systemic anti-mycobacterial immunity was associated with these skin manifestations. Methods: Within a randomized controlled BCG vaccination trial in Bangladesh, 14,828 contacts of newly diagnosed leprosy patients received BCG vaccination between 2012 and 2017 and were examined for adverse events 8 to 12 weeks post-vaccination. From a selection of vaccinated contacts, venous blood was obtained at follow-up examination and stimulated with Mycobacterium leprae (M. leprae) antigens in overnight whole-blood assays (WBA). M. leprae phenolic glycolipid-I-specific antibodies and 32 cytokines were determined in WBAs of 13 individuals with and 13 individuals without adverse events after vaccination. Results: Out of the 14,828 contacts who received BCG vaccination, 50 (0.34%) presented with adverse events, mainly (80%) consisting of skin ulcers. Based on the presence of BCG scars, 30 of these contacts (60%) had received BCG in this study as a booster vaccination. Similar to the pathological T-cell immunity observed for tuberculoid leprosy patients, contacts with adverse events at the site of BCG vaccination showed elevated IFN-γ levels in response to M. leprae-specific proteins in WBA. However, decreased levels of sCD40L in serum and GRO (CXCL1) in response to M. leprae simultaneously indicated less T-cell regulation in these individuals, potentially causing uncontrolled T-cell immunity damaging the skin. Conclusion: Skin complications after BCG vaccination present surrogate markers for protective immunity against leprosy, but also indicate a higher risk of developing tuberculoid leprosy. Clinical Trial Registration: Netherlands Trial Register: NTR3087.

Peripheral T-cell lymphoma at the injection site of influenza vaccination.

Pseudolymphomas or B-cell lymphoma at the vaccination site have been reported by several authors. However, onset of cutaneous T-cell lymphoma with cytotoxic features is a rare complication of vaccination. We report a 27-year-old man who developed a nodule and ulcer that arose at the site of injection of influenza vaccine. The neoplastic cells reacted positively for CD56, CD3, CD2, perforin, and granzyme B, but negatively for CD4, CD8, CD10, CD19, CD30, CD34, CD79, and betaF1. Molecular studies showed T-cell receptor γ (TCR-γ) chain monoclonal rearrangement. A diagnosis of peripheral T-cell lymphoma, not otherwise specified (NOS) was established. The patient had high fever, progressive liver dysfunction and a rapid fatal evolution.

Sensitization potential and reactogenicity of varying doses of BCG plus killed Mycobacterium leprae: an extended study.

This study is an extension of a previous study on an antileprosy combination vaccine of BCG plus killed Mycobacterium leprae (KML) regarding its sensitization potential and reactogenicity. The study was extended to see if by reducing the dose of BCG in the combination vaccine the incidence of suppurative adenitis could be reduced without a significant reduction in the level of postvaccination skin-test responses. The study included 860 individuals, and three preparations of the combination vaccine [BCG 0.05 mg + 6 x 10(8) KML (I), BCG 0.05 mg + 5 x 10(7) KML (II), BCG 0.01 mg + 5 x 10(7) KML (III)] along with normal saline (i.v.) were used. Each individual received one of these four preparations by random allocation. They were also tested with Rees' M. leprae soluble antigen (MLSA) and lepromin A 12 weeks after vaccination. Reactions to the MLSA were measured after 48 hr; reactions to lepromin A after 48 hr and 3 weeks. The character and size of the local response at the vaccination site were recorded at the third, eighth, and 15th week postvaccination. The results of the study showed that by halving the dose of BCG in the combination vaccine BCG plus 6 x 10(8) KML a) the incidence of suppurative regional adenitis was reduced significantly, b) there was no significant change in the post-vaccination response at 12 weeks as measured by Rees' MLSA and lepromin A, and c) the evolution of the vaccination lesion was somewhat prolonged. This dose was found satisfactory for use in a comparative antileprosy vaccine trial in South India.

Consequences of smallpox vaccination in leprosy patients.

This study illustrates the consequences of smallpox revaccination in 45 lepromatous, 28 tuberculoid, and 47 normal individuals. Results obtained with intradermal inoculations indicated that the patients with leprosy were associated with a relative anergy against the vaccinia virus, the anergy being minimal in the tuberculoid leprosy but marked in the cases with lepromatous leprosy. Major vaccinial reactions were observed more often in patients with lepromatous leprosy than in the controls or patients with tuberculoid leprosy. Furthermore in a patient with lepromatous leprosy, vaccinia necrosum also developed. The smallpox vaccination with live virus also appeared as a provocative factor for the precipitation of lepra reaction in the lepromatous leprosy cases. After 3 weeks of vaccination, the frequency of the specific humoral antibody response was the same in the tuberculoid patients and controls while it was higher in the cases with lepromatous leprosy. The prevaccination titer of total hemagglutination inhibition antibody was significantly higher in the lepromatous leprosy cases. However, the postvaccinial, humoral antibody response of the lepromatous patients was of the same magnitude as that observed in the normal individuals, and it was mainly due to a 2-mercaptoethanol-resistant antibody.

Consequences of smallpox vaccination in leprosy patients

This study illustrates the consequences of smallpox revaccination in 45 lepromatous, 28 tuberculoid, and 47 normal individuals. Results obtained with leprosy were associated with a relative anergy against the vaccinia virus, the anergy being minimal in the tuberculoid leprosy but marked in the cases with lepromatous leprosy.