Safety and efficacy of human rotavirus vaccine during the first 2 years of life in Asian infants: randomised, double-blind, controlled study.

This study evaluates the safety and efficacy against severe rotavirus gastroenteritis of the oral live attenuated human rotavirus vaccine RIX4414 (Rotarix) during the first 2 years of life in Asian infants from high-income countries. Healthy infants were enrolled to receive 2 doses of RIX4414 (N=5,359) or placebo (N=5,349). From 2 weeks post-dose 2 to 2 years of age, vaccine efficacy was 96.1% (95%CI:85.1%; 99.5%) against severe rotavirus gastroenteritis, 100% (95%CI:80.8%; 100%) against wild-type G1P[8] and 93.6% (95%CI:74.7%; 99.3%) against circulating non-G1 rotavirus types. No intussusception cases were reported within 31 days post-vaccination. RIX4414 shows a good safety profile and offers high protection during the first 2 years of life with potentially significant public health impact in this population.

Outcome of liver transplantation for children with liver disease.

INTRODUCTION: The advent of liver transplantation has revolutionised the outcome of children with both acute liver failure and chronic end-stage liver disease. The aim of this study was to review the outcome of all paediatric liver transplants performed since the National Liver Transplant Programme began in 1990. METHODS: A retrospective review of all paediatric liver transplants from 1990 to December 2004 was performed. RESULTS: 46 liver transplants were performed in 43 children, of whom 23 (53.3 percent) were female. Median age at transplant was 21 months (range 11 months to 14 years). The most common indication for liver transplant was biliary atresia (71.7 percent). Living-related transplants accounted for 63 percent (29). Re-transplant rate was 6.5 percent with allograft loss as a result of hepatic artery thrombosis (two) and hepatic vein thrombosis (one). Tacrolimus was the primary immunosuppressive agent used in 89 percent of patients, with a 19.6 percent incidence of acute allograft rejection within the first six months. There were nine deaths. They were related to portal vein thrombosis (three), chronic rejection (one), sepsis (two), post-transplant lymphoproliferative disease (two) and primary graft non-function (one). Overall actuarial one- and five-year survival rate was 85.7 percent and 81.8 percent, respectively. CONCLUSION: Liver transplantation is an established form of intervention for end-stage liver disease and a variety of liver-related metabolic disease. Our results are comparable to those of well-established liver transplant centres.

A short report on highlights of worldwide development of RIX4414: a Singaporean experience.

In Singapore, we conducted a phase II randomized, double-blind, placebo-controlled dose ranging study using an attenuated human rotavirus vaccine, RIX4414. Altogether, 2464 healthy infants were recruited. Two oral doses of vaccine at 104.7, 105.2 or 106.1 ffu or placebo were administered with routine immunizations at 3 and 4 months of age. Seroconversion and 'vaccine take' in the vaccine groups 1-month post dose 2 varied from 76 to 91% and 98 to 100% respectively. Vaccine was well tolerated and did not interfere with response of concomitantly administered vaccines.

A rotavirus vaccine for infants: the Asian experience.

INTRODUCTION: Severe rotavirus gastroenteritis in children causes significant morbidity worldwide and substantial deaths in developing countries. Hence, a live attenuated vaccine Rotarix was developed with human strain RIX4414 of G1P1A P[8] specificity. RIX4414 trials in infants have begun in developed and developing countries worldwide. An overview of RIX4414 in developed and developing countries and prospects with this vaccine in Asia are presented. METHODS: Completed RIX4414 trials have been reviewed. RESULTS: Two oral doses of RIX4414 were well tolerated with a reactogenicity profile similar to placebo. RIX4414 was also highly immunogenic, e.g., in a dose-ranging study conducted in Singapore, 98.8% to 100% of infants had a vaccine take after 2 doses. RIX4414 did not affect the immune response of simultaneously administered routine infant vaccines. RIX4414 significantly reduced severe rotavirus gastroenteritis in settings where multiple serotypes including the emerging G9 type co-circulated. CONCLUSION: These encouraging results warrant further evaluation of the vaccine worldwide and especially in developing countries with the highest need. Therefore, evaluation of the Rotarix vaccine is continuing in large phase III trials in Asia and worldwide.

Intussusception: a three-year review.

INTRODUCTION: Intussusception is the commonest cause of intestinal obstruction in infants and young children. MATERIALS AND METHODS: This report reviews the clinical presentation, investigations and outcomes of patients with intussusception treated at the KK Women's and Children's Hospital between 1 May 1997 and 30 April 2000. RESULTS: The study population comprised 160 consecutive patients treated for intussusception at our hospital over this 3-year period. The commonest symptom was vomiting; present in 135 patients (84.4%). A palpable abdominal mass was present in 90 patients (56.3%). The classical features of vomiting, abdominal pain, abdominal mass and rectal bleeding were present together in only 12 patients (7.5%). Abdominal ultrasonography was performed in 155 patients. One hundred and fifty-two patients (98.1%) had the classical target lesion on ultrasonography. Air enema reduction was attempted in all except 6 patients. In the majority of patients (130 or 84.4%), the intussusception was reduced successfully by air enema reduction. There was no association between the duration of symptoms before radiological reduction and the outcome of radiological reduction. CONCLUSIONS: As the four classical features of intussusception were present together in only 7.5% of our patients, a high index of suspicion is necessary when any of the signs and symptoms are present in an infant or young child. Abdominal ultrasonography is the diagnostic investigation of choice. Air enema reduction was successful in 84.4% of patients and the duration of symptoms did not reduce the success rate. Thus, air enema reduction should be attempted in most patients unless they have absolute contraindications.

Making the diagnosis of biliary atresia using the triangular cord sign and gallbladder length.

BACKGROUND: To evaluate the accuracy and utility of the triangular cord sign and gallbladder length in diagnosing biliary atresia by sonography. MATERIALS AND METHODS: Sixty fasted infants with cholestatic jaundice aged 2-12 weeks were examined sonographically using a 5-10 MHz linear array transducer, focusing on the triangular cord sign (as described by Choi et al. [1]), the gallbladder, and ducts. The triangular cord is defined as a triangular or tubular echogenic density seen immediately cranial to the portal vein bifurcation; it represents the fibrotic remnant of the obliterated cord in biliary atresia. The findings were blinded to blood chemistry, (99 m)Tc-DISIDA hepatobiliary scintigraphy, and liver biopsy. Diagnosis of biliary atresia was confirmed at surgery and histology. Non-biliary atresia infants resolved medically. Comparative charges of the various investigations was made. RESULTS: ++ Twelve infants had biliary atresia, and ten demonstrated a definite triangular cord. The two false-negatives had small or nonvisualized gallbladders. No false-positives were recorded. Gallbladder length ranged from 0-1.45 cm with a mean of 0. 52 cm in biliary atresia compared to a mean of 2.39 cm in nonbiliary atresia infants. (99 m)Tc-DISIDA hepatobiliary scintigraphy showed no excretion (false-positive) in 23 % of nonbiliary atresia cases. Scintigraphy and liver biopsy charges were 2 and 6 times that of sonography, respectively. CONCLUSION: The triangular cord sign and gallbladder length together are noninvasive, inexpensive, and very useful markers for biliary atresia.

Seroprevalence of antibodies against hepatitis A (anti-HAV) in Singapore: the NFDD experience.

At the 4th National Foundation for Digestive Disease (NFDD) Day in 1991 where public lectures on prevention of hepatitis and early detection of hepatocellular carcinoma were given, screening of sera obtained from 364 registrants for antibodies to Hepatitis A (IgG) was undertaken. The overall sero-prevalence rate was 50%, with 55% for males and 46% for females with antibodies for HAV. None of the subjects below 20 years old had antibodies to HAV. This rose to 16% for those 21-30 years old and 92% for those above 61 years. This study shows that in Singapore, prevalence of anti-HAV antibodies rise with age and is approaching the low endemicity pattern that is seen in developed countries.

Perineal eruption as an early sign of Kawasaki disease.

Kawasaki Disease can present as a diagnostic problem at the early stage of the disease. An interesting and distinctive perineal eruption which appeared early in the course of the disease had been reported recently but sporadically in the medical literature. We reported seven patients with Kawasaki Disease who had this perineal eruption. The rash began two to three days after the onset of fever followed by desquamation in all instances by days five to seven. When compared with other signs of Kawasaki Disease, this rash appeared early. In an earlier study done in the department, the diagnosis of Kawasaki Disease was made on an average of nine days after the onset of fever. This has an important implication as early treatment had been shown to decrease the incidence of coronary arteriectasia which is the most important complication of this disease. We believe that this distinctive perineal eruption is a valuable early clinical finding which may facilitate early diagnosis and treatment of Kawasaki Disease and unless one is aware and actively looked for the perineal eruption, this early sign may be completely missed.

Chemotherapy for hepatoblastoma in children.

Hepatoblastoma is an uncommon but highly malignant liver tumour found in childhood. It is associated with high mortality with overall survival of only 35%. Two cases of hepatoblastoma are described. Both had surgical excision of tumour with microscopic residual tumour at the resected margins. They were given adjuvant chemotherapy. Both patients are living well, disease-free and off treatment six years and two years since diagnosis.

Hepatobiliary scintigraphy in the diagnosis of biliary atresia--a Singapore experience.

In recent years, 99mTechnetium IDA hepatobiliary scintigraphy has been widely accepted as a highly sensitive and fairly accurate test in the diagnosis of biliary atresia and evaluation of neonatal jaundice. Over a period of 4 years from 1982 to 1986, a total of 110 paediatric patients had undergone 99mTechnetium IDA hepatobiliary scans in our department for prolonged neonatal jaundice. Their scans were reviewed to evaluate the role of this nuclear imaging technique in the diagnosis of biliary atresia. There were 43 true positive and 49 true negative scans. No false negative scan was encountered in our study. Hence the sensitivity was 100%. However, out of the 110 scans, there was misdiagnosis of biliary atresia in 18 cases. This gave a specificity of 73% with an accuracy of 84%. From this study we concluded that 99mTechnetium IDA imaging is a highly sensitive test in the screening of biliary atresia. However, its specificity is possibly limited by the short half life of the radioisotope 99mtechnetium in delayed 24 hr imaging and we feel that this could be improved by using slightly higher doses than what we are presently using.

Intestinal lymphangiectasia--a case report.

Primary intestinal lymphangiectasia is a rare cause of protein-losing enteropathy. We report here our first case, a young girl presenting at the age of ten months at the Department of Paediatrics, Singapore General Hospital with generalised oedema and diagnosed to have intestinal lymphangiectasia proven by intestinal biopsy. The literature on some aspects of the subjects is also reviewed.

The mortality of exchange transfusions.

A prospective study of the effect and mortality of exchange transfusion was carried out in the Kandang Kerbau Hospital, Singapore. Altogether 140 exchange transfusions were performed on 122 infants. The exchanges were done for hyperbilirubinaemia due to "idiopathic" jaundice, ABO haemolytic disease, and glucose-6-phosphate dehydrogenase deficiency. Eight infants deteriorated during the exchange, in three of whom the procedure had to be terminated prematurely. Two deaths occurred two days after the exchange--the procedure being partly responsible in one case; necrotizing enterocolitis was present in addition to the kernicterus. Exchange transfusion is not without hazards, and should be performed carefully with close monitoring of the clinical status of the infant during and immediately after the procedure.