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Background : While live attenuated BCG immunization is generally well tolerated by children, those with certain immunodeficiencies, including Mendelian susceptibility to mycobacterial disease (MSMD) are at high risk for potential adverse reactions. These can range from regional lymphadenitis to fatal disseminated BCG infection (BCGosis). Here, we describe the clinical features, investigations, and underlying primary diseases of MSMD patients in Saudi Arabia.
Methods : This case series reports a retrospective descriptive analysis of patients under 14 years of age who were diagnosed with MSMD and developed disseminated BCGitis after vaccination, between January 2009 and December 2022.
Results : Fourteen patients with disseminated BCG disease were enrolled. The most common symptom was fever, which presented in 9 (64%) of the patients, while GIT symptoms were documented in 5 (35%). The most common signs were localized lymphadenopathy, observed in 8 patients (57.1%), and hepatosplenomegaly in 6 patients (42%). All patients had evidence of Mycobacterium tuberculosis complex on culture and the majority were PCR-positive. They were all treated with anti-tuberculosis medications; in addition, 3 patients started rhIFN-γ therapy. There were 2 deaths among the 14 cases (14.3%).
Conclusion : A thorough investigation for immunological defects is crucial in children who develop disseminated BCGitis, and early anti‐mycobacterial therapy is highly recommended in MSMD patients with BCG disease.
Keywords: BCG Vaccine, Child, Genetic Predisposition to Disease, Immunologic Deficiency Syndromes, Interferon-gamma, Mycobacterium Infections
The Bacillus Calmette-Guérin (BCG) vaccine was developed in France, in 1908, by Albert Calmette and Camille Guérin. It was produced by in-vitro at- tenuation of Mycobacterium bovis strains, and first used in 1921 [1]. In 1974, the World Health Organ- ization (WHO) included the vaccine in its Ex- panded Program of Immunization (EPI) [2]. While the BCG vaccine is well tolerated by most children, it carries the risk of adverse reactions, ranging from regional suppurative lymphadenitis to fatal disseminated BCG infection (BCGosis). The estimated incidence of such reactions is 1 to 3.4 per million, with a high case-fatality ratio reaching 50-71% of cases [3,4]. Patients with Men- delian susceptibility to mycobacterial disease (MSMD) and severe combined immunodeficiency (SCID), respectively, have the highest rates of complications and mortality [5], and early anti-my- cobacterial therapy is therefore crucial in this co- hort. However, management approaches to BCG
vaccination complications remain a subject of de- bate. Here, we present cases of disseminated BCGi- tis, as well as the associated clinical and diagnostic investigations and underlying primary diseases, in a retrospective cohort of 14 MSMD patients at a single center in Saudi Arabia.
The study included data collected from January 2009 to December 2022, as part of larger study of Mycobacterial tuberculosis complex samples sub- mitted to the Microbiology Department of a single tertiary center in Saudi Arabia. All samples were from patients under 14 years of age with confirmed genetic mutations for Mendelian susceptibility to mycobacterial disease. Data were collected from the Patient Electronic Medical Record System and the Microbiology Department’s data record using a questionnaire. To ensure anonymity, no patient identifiers were used. Variables included baseline information such as sex, age, nationality, clinical symptoms, underlying primary immunodeficiency conditions, treatment, and prognosis of BCGosis in the studied patients. This case series was approved by the Institutional Review Board (IRB) on 5 May 2020 (IRB log Number 20-271). III. RESULTS
Demographics: We evaluated 14 patients with MSMD of whom 7 were male and 7 female (Table 1). Consanguinity was found in the families of 7 patients (50%). Pri- mary immunodeficiency (PID) in child relatives was confirmed in 6 cases (42.8%), and clinically suspected in 2 (14.2%). Majority of patients had re- ceived a BCG vaccination at birth, under the previ- ous Saudi national immunization plan. One patient had been vaccinated at 6 months, in accordance with the updated immunization plan, the exact tim- ing of BCG vaccination for one patient is unknown. Post-vaccination Complications: Disseminated BCG infection was diagnosed in 12 of the patients (85.7%), while 6 (42.8%) developed generalized lymphadenopathy. The most common symptom was fever, in 9 patients (64.2%). Nine pa- tients (64.2%) were screened for HIV, all were neg- ative. PCR and Culture: Samples were collected via fine-needle aspiration or swabs, depending on the site of infection and
clinical presentation (Table 2). All patients exhib- ited evidence of M. tuberculosis complex on cul- ture, and PCR testing was positive in 11 (78.5%). As all isolates were resistant to pyrazinamide, the pathogens were most likely Mycobacterium bovis BCG strains. Management and Prognosis: All patients received anti-tuberculosis medications irrespective of their diagnosis (BCGitis or BCGosis), the duration of treatment ranging from 6 months to 1.5 years or more, depending on clini- cal response. In addition, 3 patients (21.4%) started rhIFN-γ therapy out of 14 patients, and 5 patient were followed up at our hospital until the time of publication or until their death. Among the remain- ing 9 patients, 7 were lost to follow-up (some were referred for transplant). It is worth mentioning that 2 of the 14 patients (14.2%) died. Immunological Screening and Genetic Analysis: The patients’ immunological screening results are detailed in Table 3. A lymphocyte subset count was ordered for 12 patients (85.7%), and was only within normal age-specific range in 5 of the 12. Se- rum immunoglobulin levels were measured in 11 of the 14 patients (78.5%), elevated IgA levels (above 1.2 g/l) were observed in 6 patients, and el- evated IgM levels (above 1.6 g/l) were also found in 6 patients. Additionally, IgG levels exceeded the normal range (10.6 g/l) in 8 patients. Further details are provided in Table 3. The genetic analysis, conducted for all patients (Table 3), revealed an IL12B gene mutation in 6 out of 14 patients (42.8%). Three patients (P1, P12, and P14) had a STAT1 gene deletion affecting exons 3 and 4. One patient (P1) had a mutation affecting IL12RB1 , and another (P2) had a homozygous mu- tation affecting IFNGR2 . An interesting case (P11) was found to have a dual mutation affecting both interferon receptors IFNAR1 and IFNGR2 . Only three patients (P1, P7, and P13) received interferon gamma therapy. The genetic testing reports for four patients (P6, P7, P9, P10) were difficult to retrieve.
Mendelian susceptibility to mycobacterial disease (MSMD) is a rare inborn error of immunity that predisposes patients to infection by weakly virulent mycobacterial strains, such as Mycobacterium bo- vis BCG, which is the strain used in the BCG vac- cine. These patients also suffer from invasive and
tures of 16 Iranian patients with Mendelian sus- ceptibility to mycobacterial disease. Journal of Clinical Immunology . 2019 Feb 4;39(3):287–97. 9. Moorlag SJCFM, Arts RJW, van Crevel R, Netea MG. Non-specific effects of BCG vaccine on vi- ral infections. Clinical Microbiology and Infec- tion [Internet]. 2019 Dec 1 [cited 2020 May 9];25(12):1473–8. Available from: https://www.sciencedirect.com/science/arti- cle/abs/pii/S1198743X19301971 10. Sharifi Asadi P, Aghamohammadi A, Mahmoudi S, Pourakbari B, Saboui F, Mamishi S. Clinical, laboratory and imaging findings of the patients with disseminated bacilli Calmette–Guerin dis- ease. Allergologia et Immunopathologia [Inter- net]. 2015 May 1 [cited 2022 Nov 4];43(3):254– 8. Available from: https://www.elsevier.es/en-re- vista-allergologia-et-immunopathologia-105-ar- ticulo-clinical-laboratory-imaging-findings-pa- tients-S0301054614000536 11. Taur PD, Gowri V, Pandrowala AA, Iyengar VV, Chougule A, Golwala Z, et al. Clinical and mo- lecular findings in Mendelian susceptibility to mycobacterial diseases: Experience from India. Frontiers in Immunology . 2021 Feb 25;12. 12. Bernatowska E, Wolska-Kuśnierz B, Pac M, Ku- renko-Deptuch M, Pietrucha B, Zwolska Z, et al. Clinical guidelines Risk of BCG infection in pri- mary immunodeficiency children. Proposal of di- agnostic, prophylactic and therapeutic guidelines for disseminated BCG based on experience in the Department of Immunology, Children’s Memo- rial Health Institute in Warsaw between 1980- 2006. Central European Journal of Immunology . 2007 Dec 10;32(4):221–5. 13. Errami A, El Baghdadi J, Ailal F, Benhsaien I, El Bakkouri J, Jeddane L, et al. Mendelian suscepti- bility to mycobacterial disease (MSMD): Clini- cal, immunological, and genetic features of 22 patients from 15 Moroccan kindreds. Journal of Clinical Immunology . 2023 Jan 11;43(4):728–40. 14. Elsidig N, Alshahrani D, Alshehri M, Alzahrani M, Alhajjar S, Aljummah S, et al. Bacillus Calmette–Guérin vaccine related lymphadenitis in children: Management guidelines endorsed by the Saudi Pediatric Infectious Diseases Society (SPIDS). International Journal of Pediatrics and Adolescent Medicine . 2015 Jun;2(2):89–95. 15. Tan Ç, Çağdaş-Ayvaz D, Metin A, Keskin Ö, Tezcan İ, Sanal Ö. Clinical and genetic features of IL12Rb1 deficiency: Single center experience of 18 patients. The Turkish Journal of Pediatrics. 2016 Aug 25;58(4):356–61.
16. Fekrvand S, Yazdani R, Olbrich P, Gennery A, Rosenzweig SD, Condino-Neto A, et al. Primary immunodeficiency diseases and Bacillus Calmette-Guérin (BCG)-vaccine–derived com- plications: A systematic review. The Journal of Allergy and Clinical Immunology: In Practice. 2020 Apr;8(4):1371–86. 17. Kingdom of Saudi Arabia. National Tubercu- losis Program Manual, Ministry of Health. 2021.
| Clinical features | Diagnosis | Other infections | Treatment duration | Follow-up |
|---|---|---|---|---|
| (Number of anti-TB | (Prognosis) | |||
| drugs) | ||||
| Fever, cough, lym- | Dissemi- | None | 1 year | 7 years to date |
| phadenopathy, de- | nated | (Initially 4, later 2) | (Alive, good) | |
| crease appetite, | BCGosis | |||
| weight loss, hepato- | ||||
| splenomegaly | ||||
| Fever, decreased | Dissemi- | Parotitis | 1 year | lost follow-up - |
| feeding/activity, lo- | nated | (Initially 4, later 2) | referred for | |
| calized lymphade- | BCGosis | transplant | ||
| nopathy, skin rash | (Alive, good) | |||
| Left axilliary swell- | BCGitis | - | 6 months; parents | lost follow-up |
| ing | stopped medication | (Alive, good) | ||
| (Initially 2, later 2) | ||||
| Fever, generalized | Dissemi- | Recurrent infec- | Current | 3 years to date |
| lymphadenopathy, | nated | tion, incl. Salmo- | (Initially 1, later 3) | (Alive, good) |
| BCG site symptoms | BCGosis | nella lymphadeni- | ||
| tis and Salmonella | ||||
| isolated from stool | ||||
| Generalized lym- | Dissemi- | Recurrent infec- | Current | 3 years to date |
| phadenopathy, | nated | tion, incl. Salmo- | (Initially 3, later 3) | (Alive, good) |
| BCG site symptoms | BCGosis | nella Bacteremia | ||
| and Salmonella | ||||
| isolated from stool | ||||
| Fever, night sweat- | Dissemi- | Chest infections | (Initially 2, later 4) | (Died) |
| ing, cough, SOB, | nated | |||
| generalized lym- | BCGosis | |||
| phadenopathy, GIT | ||||
| symptoms, abscess, | ||||
| hepatosplenomeg- | ||||
| aly | ||||
| Diarrhea, decreased | Dissemi- | - | Unknown | Lost follow-up |
| appetite, weight | nated | (Initially 2, later 4) | (Alive, good) | |
| loss, generalized | BCGosis | |||
| lymphadenopathy, | ||||
| ascites, hepatosple- | ||||
| nomegaly | ||||
| Fever, rash, GIT | Dissemi- | Pneumonia (influ- | Unknown | Lost follow up - |
| symptoms, hepato- | nated | enza & PCP), | (Initially 4, later 4) | referred for |
| splenomegaly; pa- | BCGosis | HLH | transplant. | |
| tient also had con- | (Alive, good) | |||
| firmed TB contact. | ||||
| Law & Public Health Vol | 5, No 4. 2025 | p742 | ||
| Fever, vomiting, di- | Dissemi- | - | Unknown | Lost follow-up - |
| arrhea, GIT symp- | nated | (Initially 2, later 4) | family insisted | |
| toms, generalized | BCGosis | on discharge | ||
| lymphadenopathy | (Died) | |||
| Fever, decreased | Dissemi- | Bacteremia | Unknown | Lost follow-up |
| feeding & activity, | nated | (Klebsilla) | (Initially unknown, | (Alive, good) |
| respiratory distress, | BCGosis | later 4) | ||
| lymphadenopathy, | ||||
| hepatosplenomeg- | ||||
| aly | ||||
| Localized lymphad- | BCGitis | Recurrent infec- | Unknown | Lost follow-up |
| enopathy, rash | tion - bacterial | (Initially 3, later 3) | (Alive, good). | |
| (S.viridins), Viral | ||||
| (CMV, HSV, | ||||
| RSV), and HLH | ||||
| Prolonged fever, | Dissemi- | RSV pneumonia | 1 year | 2 years to date |
| rash, diarrhea, lo- | nated | (Initially 4, later 3) | (Alive, good) | |
| calized lymphade- | BCGosis | |||
| nopathy | ||||
| Decreased feeding, | Dissemi- | Salmonella iso- | Ongoing | 2 years to date |
| FTT, night sweat- | nated | lated from lymph | (Initially 4, later 4) | (Alive, good) |
| ing, generalized | BCGosis | node, H.pylori, | ||
| lymphadenopathy | chronic colitis | |||
| Fever, decreased | Dissemi- | Recurrent infec- | (Died) | |
| feeding, abdomen | nated | tions (viral, bacte- | (Initially 3, later 5) | |
| distension, raised | BCGosis | rial, fungal-Can- | ||
| liver enzymes, asci- | didemia), NTM | |||
| tes, hepatospleno- | co-infection | |||
| megaly, localized | ||||
| lymphadenitis |
| Sample site | Percentage |
|---|---|
| Lymph nodes | (42.8%) |
| Gastric aspirate | (64.2%) |
| Peritoneum | (21.4%) |
| Sputum | (14.2%) |
| Pleural | (7.1%) |
| BCG site | (7.1%) |
| Bone marrow | (7.1%) |
| The Journal of Medicine, Law | & Public Health Vol 5, No 4. 2025 p743 |
| No. | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 |
|---|---|---|---|---|---|---|---|
| Age (mths)* | 5 | 3 | 11 | 12 | 24 | 11 | 12 |
| WBC | 8.3 (6-17.5) | 52 (6-17.5) | 13.4 (6-17.5) | 20.6 (6-17.5) | 11.5 (6-17) | 12 (6-17.5) | 15.7 (6-17.5) |
| ALC | 4.4 (4-13.5) | 15 (4-13.5) | 8.1 (4-10.5) | 9.5 (4-10.5) | 4.4 (3-9.5) | 3 (4-10) | 5 (4-10.5) |
| CD3 | 1.9 (2.5-5.6) | 10 (2.5-5.5) | ND | 5.4 (1.9-5.9) | 4 (2.1-6.2) | 0.8 (1.9-5.9) | 1.4 (1.9-5.9) |
| CD4 | 1.5 (1.8-4) | 7.4 (1.6-4) | ND | 4.1 (1.4-4.3) | 2.5 (1.3-3.4) | 0.6 (1.4-4.3) | 0.5 (1.4-4.3) |
| CD8 | 0.3 (0.59-1.6) | 2.56 (0.56-1.7) | ND | 1 (0.5-1.7) | 1.1 (0.6-2) | 0.2 (0.5-1.7) | 0.7 (0.5-1.7) |
| CD19 | 1.2 (0.43-3) | 3.59 (0.3-2) | ND | 3.4 (0.6-2.6) | 2 (0.72-2.6) | 2 (0.6-2.6) | 1.3 (0.6-2.6) |
| IGA g/l | 1.1 (0.081-0.84) | 1.5 (0.046-0.46) | ND | 1.3 (0.16-0.84) | 1.1 (0.4-1.23) | 1.5 (0.14-0.48) | 3.3(0.16-0.84) |
| IGM g/l | 2.4 (0.3-1.08) | 0.8 (0.24-0.98) | ND | 1.7 (0.41-1.49) | 2.3 (0.48-1.68) | 2.7 (0.4-1.49) | 2.4 (0.41-1.49) |
| IGG g/l | 13.7 (1.72-8.14) | 13.6 (1.7-5.8) | ND | 20.5 (2.9-10.6) | 23 (4.2-10.5) | 14.8 (2.9-10.6) | 20 (2.9-10.6) |
| HIV | Negative | ND | ND | Negative | Negative | Negative | Negative |
| Gene | IL12RB1 | STAT1 gene dele- | IL12B | IL12B | IL12B | IL12 deficiency | IL12 deficiency |
| tion (exon 3&4) | details not found | details not found | |||||
| Mutation | c.264C>G | - | c.320dupA | c.320dup | c.320dup | - | - |
| Protein | p.Tyr88X | - | p.K107FS | p.E108Gfs*8 | p.E108Gfs*8 | - | - |
| Mutation | - | - | Heterozygous | Homozygous | Homozygous | - | - |
| Status | |||||||
| IFNγ treat- | Yes | No | No | No | No | No | Yes |
| ment | |||||||
| The | Journal of Medicine, | Law & Public Health | Vol 5, No 4. | 2025 | p744 |
| No. Patient 8 Patient 9 Patient | 10 Patient 11 Patient 12 Patient 13 Patient 14 |
|---|---|
| Age (mths)* 2 20 12 | 2 12 36 3 |
| WBC 35 (6-17.5) 10.8 (6-17) 18.2 (6-17.5) | 38.3 (6-17.5) 47 (6-17.5) 15.4 (5.5-15.5) 33.1 (6-17.5) |
| ALC 15.6 (4-13.5) 5.5 (3-9.5) 7.5 (4-10.5) | 16.9 (4-13.5) 10.2 (4-10.5) 3.9 (2-8) 5.6 (4-13.5) |
| CD3 7.5 (2.5-5.5) ND 1.5 (1.9-5.9) | 5.2 (2.5-5.5) 6.4 (1.9-5.9) 1.8 (1.4-3.7) 4.2 (2.5-5.5) |
| CD4 4.8 (1.6-4) ND 1.2 (1.4-4.3) | 1.1 (1.6-4) 4.5 (1.4-4.3) 1 (0.7-2.2) 2.6 (1.6-4) |
| CD8 2.9 (0.56-1.7) ND 0.4 (0.5-1.7) | 3.6 (0.56-1.7) 1.8 (0.5-1.7) 0.6 (0.49-1.3) 1.3 (0.56-1.7) |
| CD19 5.7 (0.3-2) ND 0.08 (0.6-2.6) | 2.3 (0.3-2) 2.2 (0.6-2.6) 1.3 (0.39-1.4) 1.3 (0.7-1.6) |
| IGA g/l ND ND <0.2 | (0.16-0.84) 0.4 (0.028-0.47) 1.1 (0.16-0.84) 4.2 (0.22-1.59) 0.98 (0.046-0.46) |
| IGM g/l ND ND <0.1 | (0.41-1.49) 0.9 (0.17-1.05) 1 (0.41-1.49) 1.9 (0.47-2) 1.56 (0.24-0.98) |
| IGG g/l ND ND 3.1 (2.9-10.6) | 6.7 (2.06-6) 20 (2.94-10.6) 22.1 (4.4-11.3) 8.3 (1.7-5.8) |
| HIV Negative Negative ND | ND Negative Negative ND |
| Gene IFNGR2 (IL12B) details (IL12B) | details not 1) IFNAR1 (deletion) STAT1 gene IL12B STAT1 gene dele- |
| not found found | 2) IFNGR2 (single deletion (exon tion (exon 3&4) |
| nucleotide deletion) 3&4) | |
| Mutation - - - | 1) c.1671_1821del - - - |
| 2) c.798delT | |
| Protein p.Y235X - - | 1) p.*557Glext*46 - p.(Glu108Glyfs*8) - |
| 2) p.C266fs | |
| Mutation Homozygous - - | Homozygous Homozygous Homozygous Homozygous |
| Status | |
| IFNγ treat- No No No | No No Yes No |
| ment | |
| *Age at first immunological screening (in months), P: | Patient, ND: not done, NR[A1] : Normal range based on age-related reference range from |
| THE HARRIET LANE HANDBOOK Twenty-first | edition - authors: Helen K. Hughes, Lauren K. Kahl. |
| E-mail: daalshahrani@kfmc.med.sa | |
| The Journal of Medicine, Law & Public Health Vol 5, No 4. 2025 | p745 |
| recurrent infections by other intracellular organ- | by Taur et al. (2021), who found lymph node sam- |
| isms such as Salmonella, Toxoplasma, Listeria, | ples culture positive for M.tuberculosis complex |
| and M. Tuberculosis [5]. Since MSMD was dis- | in 17 out of 55 patients [11]. One patient was cul- |
| covered in 1996, it has been linked to multiple | ture-positive from intra-abdominal abscess sam- |
| gene defect affecting the interferon-γ (IFN-γ). | ple, and one from a jejunal mucosal sample. Fur- |
| IL12 and IL23 signalling pathways that mediate | thermore, PCR testing was positive for M.tuber- |
| anti-mycobacterial immunity [6,7]. | culosis complex (presumed bovis) in 11 patients |
| When a microbe is engulfed by a macrophage, the | (78.5%), and ZN staining for acid-fast bacilli was |
| macrophage produces IL12 and IL23, which bind | positive in nine (64.2%). |
| to their receptors on T lymphocytes and natural | Although no current guidelines exist for the treat- |
| killer (NK) cells, stimulating the production of | ment of disseminated BCGitis in paediatric pa- |
| IFN-γ. The IFN-γ, in turn, attaches to its receptor | tients, the European Society for Immunodefi- |
| on the infected macrophage, aiding the intracellu- | ciency has established therapeutic guidelines for |
| lar killing of the microbe. The most reported type | disseminated BCG infection specific to severe |
| of MSMD is the complete or partial deficiency of | combined immunodeficiency, which recommend |
| IL12 receptor (IL12RB1) expression, which leads | treatment with four or more anti-TB agents until |
| to the inability of activated T lymphocytes and | clinical improvement is observed, followed by |
| NK cells to mount the appropriate immune re- | maintenance with two anti-TB drugs as prophy- |
| sponse to intracellular organisms [8]. | laxis until complete immune reconstitution is |
| With more than 4 billion people worldwide hav- | achieved post-hematopoietic stem cell transplan- |
| ing received the BCG vaccination, and a further | tation (HSCT) [12]. In cases where early HSCT is |
| 100 million infants receiving it every year, the | planned, a three-drug regimen may be adequate |
| vaccine ranks as one of the world’s most com- | [3]. Most of our patients were treated empirically |
| monly used [9]. Nonetheless, as a live attenuated | with three to four anti-mycobacterial drugs, with |
| vaccine, it can cause side effects ranging from lo- | treatment then modified according to sensitivity. |
| calized inflammation to widely distributed infec- | The duration of treatment ranged from 6 months |
| tions and even fatalities, especially among im- | to 1.5 years or longer, depending on clinical re- |
| munocompromised hosts [4]. Although dissemi- | sponse. Anti-mycobacterial drugs may be com- |
| nated BCG infection is a rare consequence, with | bined with other antibiotics, including ciproflox- |
| an estimated incidence of 0.14 per million vac- | acin and clarithromycin, and recombinant IFN-γ |
| cinated children, it is fatal in 50–71% of cases [5]. | treatment [13]. The choice of empirical agent, and |
| In our study, disseminated BCG infection was | the number and duration of anti-TB drugs, de- |
| documented in 14 patients (seven male and seven | pends on the patient’s susceptibility patterns, un- |
| female) following routine BCG vaccination. Gen- | derlying immunodeficiency, degree of dissemina- |
| eralized lymphadenopathy, fever, and hepatosple- | tion, and clinical response [14]. In one study, |
| nomegaly were the initial observed symptoms. In | standard anti-mycobacterial therapy was modi- |
| line with prior studies, 86% of our studied patients | fied based on drug susceptibility patterns, exclud- |
| had lymphadenopathy [10], while hepatospleno- | ing pyrazinamide; more aggressive treatment was |
| megaly was documented in 42% of our patients, | then administered over a longer duration accord- |
| also similar to other reports [3]. The prevalence of | ing to clinical response [6]. The bacillus |
| fever, rash, and gastrointestinal symptoms was | Calmette-Guérin (BCG) vaccine contains Myco- |
| 64%, 28%, and 35%, respectively. | bacterium bovis, which is intrinsically resistant to |
| The patients’ diagnosis was confirmed by TB cul- | pyrazinamide. Furthermore, different BCG |
| ture and sensitivity testing. In nine patients (64%), | strains have different susceptibility patterns; for |
| a gastric aspirate culture was positive for M.tuber- | example, the Danish strain (SSI 1331), currently |
| culosis complex (presumed bovis); two of these | used in Saudi Arabia, has low-level resistance to |
| also had positive cultures from pleural and perito- | isoniazid that may not be clinically significant, |
| neal fluid, and two also had positive cultures from | and is resistant to ethionamide. It is also important |
| respiratory and bone marrow samples. Six pa- | to consider these differences when selecting em- |
| tients (43%) ere c lt re positi e from l mph | pirical therap [14] |
| The Journal of Medicine, Law & Public Health Vol 5, No 4. 2025 | p746 |
| Most of our patients underwent surgical treatment | diseases, including primary immunodeficiencies. |
| such as lymph node excision, while two were re- | Further studies would add value by investigating |
| ferred for HSCT. Mortality was reported in 2 of | the effect of delayed BCG vaccination on the in- |
| our 14 patients (14.2%); this mortality rate is | cidence of BCG-related complications. |
| slightly higher than another study that evaluated | |
| 16 patients and reported 2 deaths due to dissemi- | VI. CONFLICT OF INTEREST |
| nated BCGosis [8]. In contrast, a study evaluating | The authors declare no conflicts of interest. |
| 18 MSMD patients reported 4 deaths from dis- | VII. REFERENCES |
| seminated BCG infection [15]. Another study of | |
| 55 MSMD patients reported mortality of 34% | 1. Milburn HJ. Primary tuberculosis. Curr Opin |
| [11], and a high mortality of 24% due to BCG in- | Pulm Med. 2001;7:133– 141. |
| fection in MSMD patients was reported in a meta- | 2. Bukhari E, Alaklobi F, Bakheet H, Alrabiaah A, |
| analysis by Fekrvand et al. [16]. | Alotibi F, Aljobair F, et al. Disseminated bacille |
| Most of our patients had a good prognosis at the | Calmette-Guérin disease in Saudi children: clini- |
| time of their most recent follow-up, with the ex- | cal profile, microbiology, immunology evalua- |
| ception of two patients who died, one of whom | tion and outcome. European Review for Medical |
| was found to have a concomitant NTM infection, | and Pharmacological Sciences [Internet]. 2016 |
| while the other, who received a BCG vaccination | Sep;20(17):3696–702. Available from: |
| at birth, presented at the age of one month and was | https://pubmed.ncbi.nlm.nih.gov/27649674/ |
| diagnosed with IL-12 deficiency. BCG-related | 3. Yue R, Chan SWB, Chew SJ, Liew WK, Thoon |
| mortality is associated with early BCG vaccina- | KC, Chong CY, et al. Disseminated bacillus |
| tion, and most of our patients were vaccinated at | Calmette-Guérin infections and primary immu- |
| birth in line with the previous Saudi national im- | nodeficiency disorders in Singapore: A single |
| munization plan. However, the plan was revised | center 15-year retrospective review International |
| according to new recommendations in August | Journal of Infectious Diseases. 2020 Jun |
| 2019, and the BCG vaccination is now adminis- | 2;97:117–25. |
| tered reduce cination [17]. at complications 6 and months minimize of age. associated BCG-related This change with BCG mortality aimed vac- to | 4. Alfawaz lated observational diatrics complications: and TS, Adolescent Alshehri study. International A M, single Medicine Alshahrani center, [Internet]. Journal D. prospective BCG of 2015 Pe- re- |
| Our study emphasizes the importance of high | Jun https://www.sciencedirect.com/science/arti- 1;2(2):75–8. Available from: |
| clinical suspicion in cases of BGC infection, and | cle/pii/S2352646715000617 |
| early duce mains treatment ric population. the initiation a need risk of disseminated of for of mortality. antimycobacterial established BCGitis Furthermore, guidelines in drugs the there paediat- for to the re- re- | 5. Mahdaviani Tabarsi bacterial with Mendelian P, treatment Moniri SA, Fallahi susceptibility A, for et BCG M, al. Jamee Effective disease to M, mycobacterial Marjani anti-myco- in patients M, |
| disease (MSMD): a case series. Ann Clin Micro- | |
| V. CONCLUSION | biol Antimicrob. 2022 Mar 1;21(1) |
| MSMD remains challenging to diagnose, particu- | 6. Ying W, Liu D, Dong X, Wang W, Hui X, Hou J, |
| larly because the presenting symptoms are usually | et delian al. Current susceptibility status of to the mycobacterial management disease of Men- in |
| delayed. In communities with a high consanguin- | mainland China. Journal of Clinical Immunol- |
| ity rate, it is worth evaluating the family history | ogy. 2019 Jul 31;39(6):600–10. |
| of PID when administering routine vaccinations. | 7. Bustamante J, Boisson-Dupuis S, Abel L, Casa- |
| Moreover, in children with disseminated BCGitis | nova JL. Mendelian susceptibility to mycobacte- |
| after BGC vaccination, a thorough investigation | rial disease: Genetic, immunological, and clinical |
| for immunological defects is crucial. Our study | features inars in Immunology. of inborn errors 2014 of IFN-γ Dec;26(6):454–70. immunity. Sem- |
| provides further insight about MSMD in TB-en- | 8. Sarrafzadeh SA, Nourizadeh M, Mahloojirad M, |
| d i t i h BCG i ti i |