Background: Disseminated Bacillus Calmette-Guérin (BCG) disease (BCGosis) is a classical feature of children with primary immunodeficiency disorders (PIDs). Methods: A 15-year retrospective review was conducted in KK Women's and Children's Hospital in Singapore, from January 2003 to October 2017. Results: Ten patients were identified, the majority male (60.0%). The median age at presentation of symptoms of BCG infections was 3.8 (0.8 -7.4) months. All the patients had likely underlying PIDSfour with Severe Combined Immunodeficiency (SCID), three with Mendelian Susceptibility to Mycobacterial Diseases (MSMD), one with Anhidrotic Ectodermal Dysplasia with Primary Immunodeficiency (EDA-ID), one with combined immunodeficiency (CID), and one with STAT-1 gain-of-function mutation. Definitive BCGosis was confirmed in all patients by the identification of Mycobacterium bovis subsp BCG from microbiological cultures. The susceptibility profiles of Mycobacterium bovis subsp BCG are as follows: Rifampicin (88.9%), Isoniazid (44.47%), Ethambutol (100.0%), Streptomycin (100.0%), Kanamycin (100.0%), Ethionamide (25.0%), and Ofloxacin (100.0%). Four patients (40.0%) received a three-drug regimen. Five patients (50.0%) underwent hematopoietic stem cell transplant (HSCT), of which three (60%) have recovered. Overall mortality was 50.0%. Conclusion: Disseminated BCG disease (BCGosis) should prompt immunology evaluation to determine the diagnosis of the immune defect. A three-drug regimen is adequate for treatment if the patient undergoes early HSCT.

Introduction: Multisystem inflammatory syndrome in children (MIS-C) is a rare inflammatory syndrome with multisystem involvement affecting children exposed to COVID-19. This condition is rarely reported in East Asia and was not detected in Singapore until 2021. We present 12 cases of MIS-C diagnosed in KK Women’s and Children’s Hospital (KKH) from October 2021 to December 2021. Method: We conducted an observational study on cases fulfilling the Singapore Ministry of Health criteria for MIS-C from January 2020 to December 2021 in KKH. Medical records were reviewed to obtain information on clinical presentation, disease course, treatment received and outcomes. Results: In the 12 cases detected, the median age was 7.50 years (interquartile range 4.00–9.25); 8 were male. All patients had mucocutaneous symptoms similar to Kawasaki disease. Other commonly involved systems were: haematological (coagulopathy 100%, lymphopaenia 91.70% and thrombocytopaenia 75.00%), gastrointestinal (75.00%) and cardiovascular (83.30%). Six patients (50.00%) had shock and were admitted to the intensive care unit. The majority of patients received treatment within 2 days of hospitalisation with intravenous immunoglobulin (IVIg) and steroids. All survived; the majority had normal echocardiograms and no long-term organ sequelae at 6 months post-discharge. Conclusion: MIS-C emerged in Singapore as the incidence of COVID-19 in the community increased in 2021. The clinical presentation of our patients is similar to earlier reports, with some significant differences from Kawasaki disease. Multidisciplinary management, timely diagnosis, and early initiation of treatment with IVIg and steroids likely contributed to comparatively good outcomes. Our cases highlight the need for continued awareness of MIS-C among physicians, and surveillance of its incidence, short- and long-term outcomes. Keywords: COVID-19, children, MIS-C, inflammation, paediatrics

IntroductionSevere Combined Immunodeficiency (SCID) is generally fatal if untreated; it predisposes to severe infections, including disseminated Bacille-Calmette-Guerin (BCG) disease from BCG vaccination at birth. However, delaying BCG vaccination can be detrimental to the population in tuberculosis-endemic regions. Early diagnosis of SCID through newborn screening followed by pre-emptive treatment with anti-mycobacterial therapy may be an alternative strategy to delaying routine BCG vaccination. We report the results of the first year of newborn SCID screening in Singapore while continuing routine BCG vaccination at birth.MethodNewborn screening using a T-cell receptor excision circle (TREC) assay was performed in dried blood spots received between 10 October 2019 to 9 October 2020 using the Enlite Neonatal TREC kit. Patients with low TREC had lymphocyte subset analysis and full blood count performed to determine the severity of lymphopenia and likelihood of SCID to guide further management.ResultsOf the 35888 newborns screened in 1 year, no SCID cases were detected, while 13 cases of non-SCID T-cell lymphopenia (TCL) were picked up. Using a threshold for normal TREC to be >18 copies/μL, the retest rate was 0.1% and referral rate to immunologist was 0.04%. Initial low TREC correlated with low absolute lymphocyte counts (ALC), and subsequent normal ALC corresponded with increases in TREC, thus patients with normal first CD3+ T cell counts were considered to have transient idiopathic TCL instead of false positive results. 7/13 (54%) had secondary TCL (from sepsis, Trisomy 21 with hydrops and stoma losses or chylothorax, extreme prematurity, or partial DiGeorge Syndrome) and 6/13 (46%) had idiopathic TCL. No cases of SCID were diagnosed clinically in Singapore during this period and for 10 months after, indicating that no cases were missed by the screening program. 8/9 (89%) of term infants with abnormal TREC results received BCG vaccination within the first 6 days of life when TREC and ALC were low. No patients developed BCG complications after a median follow-up of 17 months.ConclusionNewborn screening for SCID can be implemented while continuing routine BCG vaccination at birth. Patients with transient TCL and no underlying primary immunodeficiency are able to tolerate BCG vaccination.