Disparities in pediatric anaphylaxis triggers and management across Asia.

BACKGROUND: The epidemiology and management of anaphylaxis are not well-reported in Asia. METHODS: A regional pediatric anaphylaxis registry was established by the Asia-Pacific Research Network for Anaphylaxis (APRA), using standardized protocols for prospective data collection, to evaluate the triggers and management of anaphylaxis in the Asia-Pacific region. Pediatric patients below 18 years presenting with anaphylaxis across four Asian countries/cities (Thailand, Singapore, Hong Kong (HK), and Qingdao) were included. Allergen triggers, symptoms, anaphylaxis severity, and management were compared. RESULTS: Between 2019 and 2022, 721 anaphylaxis episodes in 689 patients from 16 centers were identified. The mean age at anaphylaxis presentation was 7.0 years (SD = 5.2) and 60% were male. Food was the most common trigger (62%), particularly eggs and cow's milk in children aged 3 years and below. In school-age children, nut anaphylaxis was most common in HK and Singapore, but was rare in the other countries, and wheat was the top allergen in Bangkok. Shellfish anaphylaxis was most common in children aged 7-17. Adrenaline was administered in 60% of cases, with 9% given adrenaline before hospital arrival. Adrenaline devices were prescribed in up to 82% of cases in Thailand but none in Qingdao. CONCLUSIONS: The APRA identified food as the main trigger of anaphylaxis in children, but causative allergens differed even across Asian countries. Fewer than two-thirds of cases received adrenaline treatment, pre-hospital adrenaline usage was low, and adrenaline device prescription remained suboptimal. The registry recognizes an unmet need to strengthen anaphylaxis care and research in Asia-Pacific.

Longitudinal assessment of antibiotic resistance gene profiles in gut microbiomes of infants at risk of eczema.

BACKGROUND: While there is increasing knowledge about the gut microbiome, the factors influencing and the significance of the gut resistome are still not well understood. Infant gut commensals risk transferring multidrug-resistant antibiotic resistance genes (ARGs) to pathogenic bacteria. The rapid spread of multidrug-resistant pathogenic bacteria is a worldwide public health concern. Better understanding of the naïve infant gut resistome may build the evidence base for antimicrobial stewardship in both humans and in the food industry. Given the high carriage rate of extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in Asia, we aimed to evaluate community prevalence, dynamics, and longitudinal changes in antibiotic resistance gene (ARG) profiles and prevalence of ESBL-producing E. coli and K. pneumoniae in the intestinal microbiome of infants participating in the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, a longitudinal cohort study of pregnant women and their infants. METHODS: We analysed ARGs in the first year of life among 75 infants at risk of eczema who had stool samples collected at multiple timepoints using metagenomics. RESULTS: The mean number of ARGs per infant increased with age. The most common ARGs identified confer resistance to aminoglycoside, beta-lactam, macrolide and tetracycline antibiotics; all infants harboured these antibiotic resistance genes at some point in the first year of life. Few ARGs persisted throughout the first year of life. Beta-lactam resistant Escherichia coli and Klebsiella pneumoniae were detected in 4 (5.3%) and 32 (42.7%) of subjects respectively. CONCLUSION: In this longitudinal cohort study of infants living in a region with high endemic antibacterial resistance, we demonstrate that majority of the infants harboured several antibiotic resistance genes in their gut and showed that the infant gut resistome is diverse and dynamic over the first year of life.

Economic value of using partially hydrolysed infant formula for risk reduction of atopic dermatitis in high-risk, not exclusively breastfed infants in Singapore.

INTRODUCTION: Previous trials have demonstrated reductions in atopic dermatitis (AD) incidence when healthy, high-risk, non-exclusively breastfed infants were fed until four months of age with 100% whey-based partially hydrolysed formula (PHF-W) versus standard cow's milk formula (CMF). We assessed the cost-effectiveness of this intervention in Singapore. METHODS: Modelling techniques were used to simulate, from birth to Month 30, the incidence and clinical/economic burden of AD in high-risk, non-exclusively breastfed infants fed with PHF-W or CMF for up to four months. Epidemiologic and clinical data were from a local comparative trial. Expert opinion informed AD treatment patterns and outcomes. Outcomes included reduction in AD risk, time spent with AD, days without AD flare, quality-adjusted life years (QALYs) and direct/indirect costs. Multivariate probabilistic sensitivity analysis was used to assess model parameter uncertainty. RESULTS: Over 30 months, with the use of PHF-W instead of CMF, the proportion of children who developed AD and the time spent with AD decreased by 16.0% (28.3% vs. 44.3%) and 6.4 months, respectively, while time without AD flare and QALYs increased by 14.9 days and 0.021 QALYs per patient, respectively. Estimated AD-related discounted costs per child for PHF-W and CMF were SGD 771 and SGD 1,309, respectively (net savings: SGD 538). PHF-W was less expensive and more effective than CMF for 73%, and cost less than SGD 50,000 per QALY for 87% of all multivariate simulations. CONCLUSION: Early short-term nutritional intervention with PHF-W instead of CMF may reduce AD incidence and costs for healthy, high-risk, non-exclusively breastfed infants in Singapore.

Cost-effectiveness of two-dose human papillomavirus vaccination in Singapore.

INTRODUCTION: Cervical cancer is the tenth most common cancer and the eighth most frequent cause of death among women in Singapore. As human papillomavirus (HPV) infection is the necessary cause of cervical cancer, the risk of cervical cancer can be substantially reduced through vaccination. This study was conducted to evaluate the cost-effectiveness of two-dose HPV vaccination as part of a national vaccination programme for 12-year-old girls in Singapore, from the perspective of the healthcare payer. METHODS: A lifetime Markov cohort model was used to evaluate the cost-effectiveness of introducing the AS04-adjuvanted HPV-16/18 vaccine (AS04-HPV-16/18v) to the current cervical screening programme in Singapore. Furthermore, the cost-effectiveness of the AS04-HPV-16/18v was compared with the HPV-6/11/16/18 vaccine (4vHPV). Model inputs were derived from local data, where possible, and validated by clinical experts in Singapore. RESULTS: Introduction of the AS04-HPV-16/18v in Singapore was shown to prevent 137 cervical cancer cases and 48 cervical cancer deaths when compared with screening alone. This resulted in an incremental cost-effectiveness ratio of SGD 12,645 per quality-adjusted life year (QALY) gained, which is cost-effective according to the World Health Organization threshold for Singapore. When discounted at 3%, AS04-HPV-16/18v was dominant over 4vHPV, with cost savings of SGD 80,559 and 28 additional QALYs gained. In the one-way sensitivity analysis, AS04-HPV-16/18v remained cost-effective compared with screening alone and dominant compared with 4vHPV. CONCLUSION: AS04-HPV-16/18v is the most cost-effective choice for reducing the burden of cervical cancer through universal mass vaccination for 12-year-old girls in Singapore.

Treatment of childhood atopic dermatitis and economic burden of illness in Asia Pacific countries.

Atopic dermatitis (AD) is a common chronic inflammatory skin condition in children. In Asia, the prevalence of AD is increasing, which is largely attributed to environmental and socioeconomic factors including family income, parental education, lifestyle and metropolitan living. Current clinical guidelines recommend a stepped approach in the management of eczema in children, with treatment steps tailored to the severity of the eczema. To address the skin barrier dysfunction, skin hydration and the application of emollients is essential. There is evidence supporting the use of bleach baths as an antimicrobial therapy against Staphylococcus aureus. In patients in whom topical treatment fails, wet wrap therapy may be considered as a treatment option before considering systemic therapies. In the second part of this article, the economic burden of AD is addressed. AD not only negatively impacts the child's quality of life but also that of the whole family and is associated with a burden on health-care costs and society. AD in an infant will lead to frequent additional visits to the pediatrician, to additional and partially expensive treatment costs and, in rare cases, to hospitalization. It is thus of utmost importance to define efficient strategies to not only treat AD but also to decrease the risk of developing the disease.

Use of intravenous immunoglobulin in an Asian paediatric population over a 10-year period.

AIMS: There is a paucity of data on the pattern of intravenous immunoglobulin (IVIG) usage in the paediatric population. This study aimed to assess the prevalence, trends, indications and burden of cost of IVIG usage in the Singaporean paediatric population. METHODS: Pharmacy data of all IVIG prescriptions between 2000 and 2009 in the two major paediatric public hospitals in Singapore were retrospectively reviewed. Each prescription was cross-referenced with the patient's hospital records to confirm the administration of IVIG and indication of use. RESULTS: Over the 10-year period, a total 78,155 g of IVIG valued at an estimated $5.2 million was prescribed. There was an increasing trend of 445.6 g/year (P = 0.02) over this period. Analysis of patients showed that the most common indication for IVIG use was Kawasaki disease, both in terms of the proportion of patients (60%) and amount of IVIG used (34%). Kawasaki disease was also the only indication where there were significant increasing trends in both patient numbers (7.4 patients/year) and amount of IVIG used (247.5 g/year). The indications with the highest amount of IVIG used per patient were for conditions related to primary immunodeficiency diseases and stem cell transplantation, where repeat transfusions were required. More than 75% of indications were Food and Drug Administration approved. CONCLUSION: Albeit substantial and increasing, the use of IVIG in Singaporean children is mostly evidence based.

Evaluation of stool microbiota signatures in two cohorts of Asian (Singapore and Indonesia) newborns at risk of atopy.

BACKGROUND: Studies have suggested that demographic and lifestyle factors could shape the composition of fecal microbiota in early life. This study evaluated infant stool microbiota signatures in two Asian populations, Singapore (n = 42) and Indonesia (n = 32) with contrasting socioeconomic development, and examined the putative influences of demographic factors on these human fecal associated bacterial signatures. RESULTS: Longitudinal analysis showed associations of geographical origin with Clostridium leptum, Atopobium and Bifidobacterium groups. Mode of delivery had the largest effect on stool microbiota signatures influencing the abundance of four bacterial groups. Significantly higher abundance of bacterial members belonging to the Bacteroides-Prevotella, Bifidobacterium and Atopobium groups, but lower abundance of Lactobacilli-Enterococci group members, were observed in vaginal delivered compared to caesarean delivered infants. Demographic factors influencing the structure of infants stool microbiota during the first year of life included breastfeeding, age of weaning, sibship size and exposure to antibiotics. CONCLUSIONS: Differences in stool microbiota signatures were observed in relation to various demographic factors. These features may confound studies relating to the association of the structure of fecal microbiota and the predisposition to human modern disease.

Allergies in Asia: differences in prevalence and management compared with western populations.

There is wide variability in the epidemiology and management of childhood asthma and related atopic diseases globally. Urbanized, affluent Western countries tend to have a higher prevalence of these diseases compared with Asian nations. However, recent studies have shown that the prevalence in Asia is increasing, although the rate of increase has slowed in the more developed Asian cities. Some possible causes for these differences are socioeconomic status, degree of urbanization, rates of infection, healthcare practices and genetic factors. Importantly, there are significant differences in the way asthma and allergic diseases are managed within Asia. This is of great concern because of the health implications, as these diseases are some of the most common chronic conditions that affect both adults and children. This review compares the differences in prevalence and management between Asia and the West, and discusses some of the possible reasons behind these variations.

Hierarchical oligonucleotide primer extension as a time- and cost-effective approach for quantitative determination of Bifidobacterium spp. in infant feces.

The Bifidobacterium spp. present in 10 infant fecal samples (4 from infants with eczema and 6 from healthy infants) were quantified with both hierarchical oligonucleotide primer extension (HOPE) and fluorescence in situ hybridization-flow cytometry. The relative abundances of Bifidobacterium longum and B. catenulatum with respect to the total bifidobacteria had a poor correlation (rho, <0.600; P value, >0.208), presumably due to differences in primer specificity and the level of hybridization stringency of both methods. In contrast, the relative abundances of organisms of the genus Bifidobacterium against the total amplified 16S rRNA genes and those of B. adolescentis, B. bifidum, and B. breve against the genus Bifidobacterium exhibited a good statistical correlation (rho, >0.783; P value, <0.066). This good comparability supports HOPE as a method to achieve high-throughput quantitative determination of bacterial targets in a time- and cost-effective manner.