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>

Right-siting chronic kidney disease care-a survey of general practitioners in Singapore

<p><b>INTRODUCTION</b>Chronic kidney disease (CKD) is a major public health problem in Singapore. Efforts are being made to right-site CKD care (stage 1 to 3) from specialist outpatient clinics (SOCs) to general practitioners (GPs) to ease congestion. This study aims to identify factors influencing screening and management of CKD among GPs in Singapore.</p><p><b>MATERIALS AND METHODS</b>A survey was conducted among the 1202 GPs between April and September 2010. The survey questionnaire was developed in collaboration with experts in nephrology and general practice, it included questions about screening, awareness and management of CKD.</p><p><b>POPULATION STUDIED</b>GPs registered with the National Healthcare Group General Practitioner (NHG GP) partner database.</p><p><b>RESULTS</b>Three hundred and two GPs completed the survey. A total of 70% of the respondents were males and with their median years of practice as 18. A total of 86% of them reported screening for CKD while 50% of GPs were confident of managing patients with CKD stage 1; and 38% of GPs are aware of CKD guidelines. Majority of GPs (64%) agreed that right-siting of early CKD patients would ease congestion at SOCs. Some of the obstacles in CKD management listed by the GPs were lack of patient trust, experience and communication with the specialist and the inability of the patient to pay.</p><p><b>CONCLUSION</b>GPs screen patients for CKD, however their awareness of guidelines is limited. Opportunities exist for improving physician recognition of CKD, awareness of CKD guidelines, improving collaborative care and reimbursement for the patient and the provider. This study has identified factors which when addressed could lead to wider acceptance of CKD right-siting by both the patients and the GPs.</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>

Primary vaccination of infants against hepatitis B can be completed using a combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Haemophilus influenzae type B vaccine

<p><b>INTRODUCTION</b>Children in Singapore receive vaccination against hepatitis B virus (HBV) at 0, 1 and 5 or 6 months of age, and vaccination against pertussis, diphtheria, tetanus, and polio at 3, 4 and 5 months of age. Parents often choose to vaccinate with the combined acellular-pertussis-inactivated polio-Hib vaccine (DTPa-IPV/Hib). We investigated whether a combined hexavalent vaccine, DTPa-HBV-IPV/Hib, could replace the separate administration of DTPa-IPV/Hib and HBV for the final vaccination at 5 months of age (Trial DTPa-HBV-IPV-075).</p><p><b>MATERIALS AND METHODS</b>In an open study, 150 children were randomised to complete their vaccination schedule with DTPa-IPV/Hib + HBV or DTPa-HBV-IPV/Hib.</p><p><b>RESULTS</b>One month after the final vaccination, there was no difference between groups in seroprotection rates or antibody concentrations against HBV. Seroprotection rates against diphtheria, tetanus, Hib and polio, as well as vaccine response rates to pertussis antigens were also similar between groups. Local and general symptoms occurred at a similar rate after the third dose of either vaccine.</p><p><b>CONCLUSION</b>The immunogenicity and reactogenicity of the hexavalent vaccine DTPa-HBV-IPV/Hib (Infanrix hexa, GSK) group is comparable to that of separately administered DTPa-IPV/Hib and HBV vaccines. Combined hexavalent vaccine, DTPa-HBV-IPV/Hib, could replace the separate administration of DTPa-IPV/Hib and HBV for vaccination at 5 months of age, thereby reducing the number of injections required.</p>

Safety, reactogenicity and immunogenicity of the live attenuated combined measles, mumps and rubella vaccine containing the RIT 4385 mumps strain in healthy Singaporean children

<p><b>INTRODUCTION</b>Measles, mumps and rubella (MMR) are viral infections causing significant mortality and morbidity for which effective and safe vaccines are available. The safety, reactogenicity and immunogenicity of a combined MMR vaccine when administered to healthy Singaporean children were evaluated in this study.</p><p><b>MATERIALS AND METHODS</b>A total of 150 children aged 12 to 18 months were vaccinated in this open, single-group, single-centre study [209762/147]. Solicited local and general symptoms reported within 4 days of vaccination and fever, parotid/salivary gland swelling and signs of meningism in the 43 days following vaccination were recorded using diary cards. Serious adverse events occurring during the study period were monitored. Immunogenicity was assessed at 42 days post-vaccination.</p><p><b>RESULTS</b>Redness (8.7%) and pain (7.2%) at injection site were the most commonly reported solicited local symptoms during the 4-day follow-up period after vaccination. Percentage of subjects reporting drowsiness, irritability and loss of appetite during the 4-day follow-up after vaccination was 7.2%, 8% and 7.2%, respectively. None of the solicited symptoms reported during the 4-day follow-up period was of grade "3" intensity. Fever (42.8%) was the most commonly reported solicited general symptom, with 5.1% of the children reporting fever >39.0 degrees C (axillary). No serious adverse events considered to be related to vaccination were reported. Seroconversion rates were 100% for measles and rubella antibodies and 98.1% for mumps antibodies.</p><p><b>CONCLUSIONS</b>GlaxoSmithKline Biologicals' MMR vaccine was shown to be well tolerated and highly immunogenic when used in Singaporean children 12 to 18 months of age.</p>