Clinical profile and outcome of clinical BCG disease in infants

Indumathi, C K; Kowtal, Priyadarashini M.; Poornima, R; Lewin, Sanjiv

doi:10.1007/s13312-014-0491-z

Cited by 10 publications

(10 citation statements)

References 5 publications

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“…Although Inborn Errors of Immunity (IEI) as a group have been traditionally described to cause susceptibility to a wide range of micro-organisms, MSMD causes predisposition to infection by selective intracellular organisms. BCG related complications may be the presenting manifestation in MSMD in 4-80% of the patients (15). The practice of vaccinating all babies soon after birth might be the reason for an early presentation seen in our cohort; in addition to other well-known social factors like high population density, high incidence of M. tb in the country, poor nutrition, and unhygienic conditions.…”

Section: Discussionmentioning

confidence: 70%

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Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India

et al. 2021

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Mendelian Susceptibility to Mycobacterial diseases (MSMD) are a group of innate immune defects with more than 17 genes and 32 clinical phenotypes identified. Defects in the IFN-γ mediated immunity lead to an increased susceptibility to intracellular pathogens like mycobacteria including attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains and non-tuberculous environmental mycobacteria (NTM), Salmonella, fungi, parasites like Leishmania and some viruses, in otherwise healthy individuals. Mutations in the IL12RB1 gene are the commonest genetic defects identified. This retrospective study reports the clinical, immunological, and molecular characteristics of a cohort of 55 MSMD patients from 10 centers across India. Mycobacterial infection was confirmed by GeneXpert, Histopathology, and acid fast bacilli staining. Immunological workup included lymphocyte subset analysis, Nitro blue tetrazolium (NBT) test, immunoglobulin levels, and flow-cytometric evaluation of the IFN-γ mediated immunity. Genetic analysis was done by next generation sequencing (NGS). Disseminated BCG-osis was the commonest presenting manifestation (82%) with a median age of presentation of 6 months due to the practice of BCG vaccination at birth. This was followed by infection with Salmonella and non-typhi Salmonella (13%), Cytomegalovirus (CMV) (11%), Candida (7%), NTM (4%), and Histoplasma (2%). Thirty-six percent of patients in cohort were infected by more than one organism. This study is the largest cohort of MSMD patients reported from India to the best of our knowledge and we highlight the importance of work up for IL-12/IL-23/ISG15/IFN-γ circuit in all patients with BCG-osis and suspected MSMD irrespective of age.

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Section: Discussionmentioning

confidence: 70%

“…There is a paucity of literature on MSMD from India with only a few published case reports (12)(13)(14)(15). In this study, we report clinical, immunological, and molecular characteristics of a retrospective cohort of 55 MSMD patients from 10 centers across India.…”

Section: Introductionmentioning

confidence: 97%

Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India

et al. 2021

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“…The positive predictive value of BCG‐itis in predicting an underlying IEI is 32.6% as depicted in Table . The lower predictive value of BCG‐itis can be explained by the fact that non‐suppurative lymphadenitis may be considered part of the normal course of BCG vaccination and resolves spontaneously over a few weeks to months 35 …”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…A study from India reported that 75% of infants with BCG-related disease have regional or localized involvement, whereas only 25% had disseminated disease. 14 Among patients with disseminated disease, only one patient had IFNγ-R1 gene mutation. 14 The use of two different strains for vaccination in the same population, one with and the other without the mpb64 gene, further complicates the problem of identification.…”

Section: Discussionmentioning

confidence: 99%

BCG Infection due to MPT64-Negative Strain: A Diagnostic Challenge

Suresh

Biswas

Prasad

et al. 2020

The American Journal of Tropical Medicine and Hygiene

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MPT64 is a 24-kDa immunogenic protein that is widely used as a diagnostic marker for the differentiation of Mycobacterium tuberculosis complex (MTBC) from nontuberculous Mycobacterium (NTM). Unlike Mycobacterium bovis, Bacillus Calmette-Guerin (BCG) vaccine strains with RD2 deletion do not secrete MPT64. Culture isolates from infections due to these strains may be falsely identified as nontuberculous Mycobacterium in the absence of clinical correlation. Here, we present one case each of BCG adenitis and osteitis, both of which were considered as MPT64 card-negative Mycobacterium spp. (i.e., NTM) and were later identified as M. bovis BCG Danish 1331 strain. The first case was a 4-month-old female infant admitted with swollen lymph nodes in the left supraclavicular and the left axillary region of 1 month duration. The second case was of a 1-year-and-5-month-old male child who presented with a limp on the left leg and soft tissue swelling of 1 month duration on the anterolateral aspect of the left knee joint. In both cases, BCG vaccine was administered at birth on the left deltoid region and had healed without any complication. Clinical samples in both cases were positive by Xpert tuberculosis/ RIF for MTBC, and cultures grew acid-fast bacilli which were negative by MPT64 assay. The clinical implication of infections due to M. bovis BCG is immense as they are inherently resistant to pyrazinamide, and the presence of disseminated BCG infection in young children is a hallmark of serious immune deficiency which needs to be ruled out.

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Clinical profile and outcome of clinical BCG disease in infants

Cited by 10 publications

References 5 publications

Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India

Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India

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

BCG Infection due to MPT64-Negative Strain: A Diagnostic Challenge

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