Analysis of Cholangitis Rates with Extended Perioperative Antibiotics and Adjuvant Corticosteroids in Biliary Atresia / 대한소아소화기영양학회지

Purpose@#There is no consensus regarding adjuvant therapies following Kasai portoenterostomy (KP) for biliary atresia (BA). This study aimed to analyze the effect of extended perioperative intravenous antibiotics (PI-Abx) and adjuvant corticosteroid on cholangitis and jaundice clearance rates in the 3 years post-KP in children with BA. @*Methods@#Data of patients who underwent KP between 1999-2018 at a single center were retrospectively analyzed. Group A (1999–2010) received PI-Abx for 5 days, Group B (2010–2012) received PI-Abx for 5 days plus low-dose prednisolone (2 mg/kg), and Group C (2012–2017) received PI-Abx for 14 days plus high-dose prednisolone (5 mg/kg). @*Results@#Fifty-four patients were included with groups A, B, and C comprising 25, 9, and 20 patients, respectively. The number of episodes of cholangitis was 1.0, 1.6, and 1.3 per patient (p=NS) within the first year and 1.8, 2.3, and 1.7 (p=NS) over 3 years in Groups A, B, and C, respectively. The jaundice clearance rate at 6 months was 52%, 78%, and 50% (p=NS), and the 3-year native liver survival (NLS) rate was 76%, 100%, and 80% (p=NS) in Groups A, B, and C, respectively. A near-significant association was observed between the incidence of cholangitis within the first year and decompensated liver cirrhosis/death at 3 years post KP (p=0.09). Persistence of jaundice at 6 months was significantly associated with decompensated cirrhosis/death at 3 years (p<0.001). @*Conclusion@#The extended duration of PI-Abx and adjuvant corticosteroids was not associated with improved rates of cholangitis, jaundice clearance, or NLS in patients with BA.

Analysis of Cholangitis Rates with Extended Perioperative Antibiotics and Adjuvant Corticosteroids in Biliary Atresia / 대한소아소화기영양학회지

Purpose@#There is no consensus regarding adjuvant therapies following Kasai portoenterostomy (KP) for biliary atresia (BA). This study aimed to analyze the effect of extended perioperative intravenous antibiotics (PI-Abx) and adjuvant corticosteroid on cholangitis and jaundice clearance rates in the 3 years post-KP in children with BA. @*Methods@#Data of patients who underwent KP between 1999-2018 at a single center were retrospectively analyzed. Group A (1999–2010) received PI-Abx for 5 days, Group B (2010–2012) received PI-Abx for 5 days plus low-dose prednisolone (2 mg/kg), and Group C (2012–2017) received PI-Abx for 14 days plus high-dose prednisolone (5 mg/kg). @*Results@#Fifty-four patients were included with groups A, B, and C comprising 25, 9, and 20 patients, respectively. The number of episodes of cholangitis was 1.0, 1.6, and 1.3 per patient (p=NS) within the first year and 1.8, 2.3, and 1.7 (p=NS) over 3 years in Groups A, B, and C, respectively. The jaundice clearance rate at 6 months was 52%, 78%, and 50% (p=NS), and the 3-year native liver survival (NLS) rate was 76%, 100%, and 80% (p=NS) in Groups A, B, and C, respectively. A near-significant association was observed between the incidence of cholangitis within the first year and decompensated liver cirrhosis/death at 3 years post KP (p=0.09). Persistence of jaundice at 6 months was significantly associated with decompensated cirrhosis/death at 3 years (p<0.001). @*Conclusion@#The extended duration of PI-Abx and adjuvant corticosteroids was not associated with improved rates of cholangitis, jaundice clearance, or NLS in patients with BA.

Efficacy, Immunogenicity and Safety of a Human Rotavirus Vaccine RIX4414 in Singaporean Infants

<p><b>INTRODUCTION</b>This was the first study conducted to evaluate the efficacy of 2 oral doses of the human rotavirus vaccine, RIX4414 in Singaporean infants during the first 3 years of life.</p><p><b>MATERIALS AND METHODS</b>Healthy infants, 11 to 17 weeks of age were enrolled in this randomised (1:1), double-blinded, placebo-controlled study to receive 2 oral doses of RIX4414 vaccine/placebo following a 0-, 1-month schedule. Vaccine efficacy against severe rotavirus (RV) gastroenteritis (Vesikari score ≥11) caused by wild-type RV strains from a period starting from 2 weeks post-Dose 2 until 2 and 3 years of age was calculated with 95% confidence interval (CI). Immunogenicity and safety of the vaccine were also assessed.</p><p><b>RESULTS</b>Of 6542 infants enrolled, 6466 were included in the efficacy analysis and a subset of 100 infants was included in the immunogenicity analysis. Fewer severe RV gastroenteritis episodes were reported in the RIX4414 group when compared to placebo at both 2 and 3 year follow-up periods. Vaccine efficacy against severe RV gastroenteritis at the respective time points were 93.8% (95% CI, 59.9 to 99.9) and 95.2% (95% CI, 70.5 to 99.9). One to 2 months post-Dose 2 of RIX4414, 97.5% (95% CI, 86.8 to 99.9) of infants seroconverted for anti-RV IgA antibodies. The number of serious adverse events recorded from Dose 1 until 3 years of age was similar in both groups.</p><p><b>CONCLUSION</b>Two oral doses of RIX4414 vaccine was immunogenic and provided high level of protection against severe RV gastroenteritis in Singaporean children, during the first 3 years of life when the disease burden is highest.</p>

Prolonged hepatitis and jaundice: a rare complication of paediatric Epstein-Barr virus infection

We herein report the case of a 14-year-old girl with Epstein-Barr virus (EBV) infectious mononucleosis who developed prolonged hepatitis and jaundice. At presentation, she had tender hepatomegaly with a markedly deranged liver function test. Abdominal ultrasonography showed hepatomegaly and a thickened gallbladder wall. During the subsequent 11 weeks, her transaminases showed two further peaks, which corresponded with clinical deterioration. Her highest alanine transaminase level was 1,795 µ/L and total bilirubin level was 154 µmol/L. She recovered fully with conservative management. EBV-related liver involvement is typically mild and self-limiting. We believe that tender hepatomegaly and gallbladder thickening may be important predictors of significant liver involvement. Although multiple transaminase peaks may occur, we do not consider this an indication for antiviral or immunosuppressive therapy. In the absence of strong evidence supporting the use of any specific therapy, we recommend a conservative approach for an immunocompetent patient.

Paediatric inflammatory bowel disease in a multiracial Asian country

<p><b>INTRODUCTION</b>This study examined the characteristics and trends in the incidence of inflammatory bowel disease (IBD) among children in Singapore.</p><p><b>METHODS</b>We retrospectively reviewed all patients under 18 years diagnosed with IBD over a 14-year period. Information on demographics, disease presentation, laboratory findings, radiological investigations, and endoscopic and histological findings were obtained from the patients' medical records.</p><p><b>RESULTS</b>32 patients were diagnosed with IBD, 30 of whom had Crohn's disease and 2 had ulcerative colitis. The incidence of IBD rose from an initial rate of 2.2 per 100,000 patients in the year 2000 to a peak of 11.4 patients per 100,000 patients by 2008. Median age of onset of symptoms was 10.5 years. There were more boys (63%) than girls in the group and a higher representation of Indians (34.4%). The most common presenting symptoms were abdominal pain (87.5%), diarrhoea (75.0%) and weight loss (71.9%). Extraintestinal manifestations such as fever and arthralgia were found in over 50% of patients. The most common physical findings were perianal abnormalities (56.3%), mouth ulcers (37.5%) and growth failure (15.6%). Abnormal laboratory findings such as low albumin, raised erythrocyte sedimentation rate, anaemia, thrombocytosis and high C-reactive protein were found in nearly half of the patients. Endoscopic and histological findings showed that a majority of patients (90.6%) also had evidence of inflammation in the upper gastrointestinal tract.</p><p><b>CONCLUSION</b>Paediatric IBD is on the rise. The higher occurrence in Indians, earlier onset and more florid presentation may suggest different genetic and environmental influences specific to Asian children.</p>

An update of paediatric intussusception incidence in Singapore: 1997-2007, 11 years of intussusception surveillance

<p><b>INTRODUCTION</b>Understanding baseline epidemiology of intussusception (IS) in different geographical settings is important for the safety assessment of rotavirus vaccines. This paper presents IS surveillance data from Singapore between 1997 and 2007, including the period between November 2005 and December 2007 when rotavirus vaccines (primarily Rotarix) were available to newborns in Singapore.</p><p><b>MATERIALS AND METHODS</b>Case ascertainment, collection, analyses and presentation of IS data was done as per recommendations of the Brighton Collaboration Working Group. For estimating the IS incidence rate in infants, live births for the years of the study were used as denominators, while for incidence in children age <2 years, the expected numbers of infant deaths occurring between 1 and 2 years of age was deducted from the combined live births for the 2 years, to obtain the denominator.</p><p><b>RESULTS</b>The incidence of IS among children aged <1 year throughout this 10-year period was higher than the incidence of IS in children between 1 and 2 years of age. In 2005, 2006 and 2007, the incidence of IS per 100,000 was 39.9, 26.4 and 35.6 in children aged <1 year and 26.2, 23.8 and 28.7 in children <2 years.</p><p><b>CONCLUSION</b>This IS surveillance study provides reassuring preliminary evidence that there is no increase in the incidence of IS in Singapore after the introduction of rotavirus vaccines (including Rotarix) in Singapore.</p>

Immunogenicity, reactogenicity and safety of a diphtheria-tetanus-acellular pertussis-inactivated polio and Haemophilus influenzae type b vaccine in a placebo-controlled rotavirus vaccine study

<p><b>INTRODUCTION</b>In recent years, acellular pertussis combination vaccines have facilitated compliance with and coverage of the national immunisation programme in Singapore. This phase-II study (Rota-007) evaluated the immunogenicity, reactogenicity and safety of a DTPa-IPV/Hib combined vaccine when co-administered with a rotavirus vaccine.</p><p><b>MATERIALS AND METHODS</b>A total of 2464 children aged 3 months were vaccinated with DTPa-IPV/Hib together with a randomised 1:3 ratio of either placebo (n=653) or 1 of 3 different formulations of a rotavirus vaccine. Blood samples were collected for immunogenicity analysis 1 month after the third DTPa-IPV/Hib vaccine dose in a subset of subjects (n = 640). Local and general reactogenicity and unsolicited adverse events were recorded during the follow-up after each vaccination.</p><p><b>RESULTS</b>Serological analysis showed >95% response for all antigens in the co-administered DTPa-IPV/Hib vaccine, with no difference between the rotavirus vaccine and placebo groups. No differences in adverse events and reactogenicity were reported in the rotavirus vaccine and placebo groups. Only 0.2% of the subjects reported Grade 3 adverse events. Three subjects (from the vaccine groups) died during the study, which were assessed by the investigators as unrelated to vaccination. No deaths were reported in the placebo group.</p><p><b>CONCLUSION</b>The combined DTPa- IPV/Hib vaccine is safe, well tolerated and highly immunogenic when given alone or coadministered with the rotavirus vaccine for infants in Singapore.</p>

The epidemiology of paediatric intussusception in Singapore: 1997 to 2004

<p><b>INTRODUCTION</b>The world's first rotavirus vaccine, Rotashield or RRV-TV, was registered in the US in 1998, but withdrawn within a year because of an observed association with intussusception (IS). Surveillance for IS has consequently become important in safety monitoring of new-generation rotavirus vaccines during development. Post-marketing surveillance is also important, and requires the availability of local baseline epidemiology data on IS.</p><p><b>MATERIALS AND METHODS</b>An eight-year study of IS in children under 2 years of age in Singapore was performed by retrospective review of admissions to KK Women's and Children's Hospital, the main paediatric hospital, from 1997 to 2001, followed by prospective surveillance of all hospitals from 2001 to 2004, using the case definition of the Brighton Collaboration Intussusception Working Group.</p><p><b>RESULTS</b>The average IS incidence was 60 per 100,000 in under-ones, and 32 per 100,000 in under-twos, with a downward trend between 1999 and 2004. Ninety-two per cent of subjects were aged below one year, with 51% aged 6 months to 11 months. The mean age at which IS occurred increased from 6.4 months to 12.5 months over the study period. The male-to-female ratio was 1.3:1. No trend in IS numbers was observed over different months of the year.</p><p><b>CONCLUSION</b>IS in Singapore shows no seasonality, but has demonstrated a trend of decreasing incidence in recent years. While highest in the first year of life, the risk of IS is increasing in the second year of life. Males have a slightly higher risk.</p>