The impact of rotavirus vaccination on acute diarrhea in Thai children under 5 years of age in the first year of universal implementation of rotavirus vaccines in the National Immunization Program (NIP) in Thailand: a 6-year analysis.

BACKGROUND: Two types of rotavirus vaccines (RVs), Rotarix (RV1) and RotaTeq (RV5), were licensed as optional vaccines in 2012 and became part of the National Immunization Program (NIP) in the fiscal year 2020 in Thailand. The main objective was to evaluate the impact of rotavirus vaccines on the burden of acute diarrheal severity ranging from outpatient visits, diarrheal-related admission or deaths in the pre-NIP period (fiscal year 2015-2019) and in the fiscal year 2020. The minor objectives were assessed on the monthly admission rate, rotavirus vaccine coverage rate and rotavirus vaccine completed dose (RotaC). METHODS: Data regarding OPD, admission, and death cases under the Thailand National Health Coverage (NHC) from fiscal year 2015-2020, which were recorded as International Classification of Diseases and Related Health Problem 10th (ICD-10), were analyzed. RESULTS: The burden of diarrheal-related disease diminished after the rotavirus vaccine was introduced in the fiscal year 2020 when compared to the previous 5 fiscal years. The OPD visit rate decreased from 10.1 to 8.3 visits per 100 person-years (P < 0.001), or a 17.8% reduction (incidence rate ratio (IRR) = 0.82; 95% confidence interval (CI): 0.81 to 0.82). The admission rate significantly declined from 31.4 to 30.5 cases per 1,000 person-years, (P < 0.001), or a 2.9% reduction (IRR = 0.97; 95% CI: 0.96 to 0.98). The diarrheal-related mortality rate also subsided from 10.2 to 8.1 cases per 100,000 person-years (P 0.3), or a 20.0% reduction (IRR = 0.88; 95% CI: 0.50 to 1.22). The major population in both admissions and deaths was infants under 1 year of age (P < 0.001). Seasonality was seen as a constant bimodal pattern, with a significant decrease in monthly admissions after 6 months of rotavirus vaccine introduction to NIP (P < 0.001). RotaC was 37.4% in the first year of NIP. CONCLUSIONS: The rotavirus vaccine had a potential benefit for reducing the diarrheal disease burden, especially in infants under one year of age. Seasonality outbreaks of acute diarrhea subsided after the rotavirus vaccine was introduced. The RotaC was fairly low in the first year of the NIP. The quality of the rotavirus vaccine should be warranted. TRIAL REGISTRATION: Number TCTR20220120003 , date of registration: 20/01/2022, site: Thai Clinical Trials Registry.

Bone Mineral Density and Dickkopf-1 in Adolescents with Non-Deletional Hemoglobin H Disease.

BACKGROUND: Low bone mineral density (BMD) is prevalent in individuals with ß-thalassemia and is associated with increased circulating dickkopf-1 concentration. These data are limited in α-thalassemia. Therefore, we aimed to determine the prevalence of low BMD and the association between BMD and serum dickkopf-1 in adolescents with non-deletional hemoglobin H disease, a form of α-thalassemia whose severity is comparable to ß-thalassemia intermedia. METHODOLOGY: The lumbar spine and total body BMD were measured and converted into height-adjusted z-scores. Low BMD was defined as BMD z-score ≤ -2. Participant blood was drawn for measurement of dickkopf-1 and bone turnover marker concentrations. RESULTS: Thirty-seven participants with non-deletional hemoglobin H disease (59% female, mean age 14.6 ± 3.2 years, 86% Tanner stage ≥2, 95% regularly transfused, 16% taking prednisolone) were included. Over one year prior to the study, mean average pretransfusion hemoglobin, ferritin and 25-hydroxyvitamin D concentrations were 8.8 ± 1.0 g/dL, and 958 ± 513 and 26 ± 6 ng/mL, respectively. When participants taking prednisolone were excluded, the prevalence of low BMD at the lumbar spine and total body was 42% and 17%, respectively. BMD at both sites was correlated positively with body mass index z-score, and negatively with dickkopf-1 (all p-values <0.05). There were no correlations among dickkopf-1, 25-hydroxyvitamin D, osteocalcin and C-telopeptide of type-I collagen. Multiple regression analysis showed dickkopf-1 inversely associated with total body BMD z-score adjusting for sex, bone age, body mass index, pre-transfusion hemoglobin, 25-hydroxyvitamin D, history of delayed puberty, type of iron chelator and prednisolone use (p-value = 0.009). CONCLUSIONS: We demonstrated a high prevalence of low BMD in adolescents with non-deletional hemoglobin H disease. Moreover, dickkopf-1 inversely associated with total body BMD suggesting it may serve as a bone biomarker in this patient population.

Burden and pattern of acute diarrhea in Thai children under 5 years of age: a 5-year descriptive analysis based on Thailand National Health Coverage (NHC) data.

BACKGROUND: The incidence of acute diarrhea in Thai children under five years of age has increased over the last three decades. Even though mortality has significantly declined, the burden and cost of medical treatment are still high. Our objectives are to describe the burden and pattern of acute diarrhea cases that required admissions by Thai children under five years of age from 2015 to 2019. METHODS: Data regarding the admission of acute diarrhea cases of Thai children with Thailand National Health Coverage (NHC) under five years of age from 2015 to 2019, recorded as International Statistical Classification of Diseases and Related Health Problems, tenth Revision, Thai Modification (ICD-10-TM), were analyzed. RESULTS: The incidence trend of yearly acute diarrhea in children 0-5 years of age slightly increased from 33.36 cases per 1,000 population in 2010 to an average of 33.79 cases per 1,000 population/ year from 2015 to 2019 or approximately 0.43 cases per 1,000 population over the last decade while diarrhea-related mortality had a low, constant rate of 0.71 to 1.16 per 100,000 population per year. Two thirds of the mortality rate was observed in children under 1 year of age or 4.1 cases per 100,000 person-years in 5-year period (P < 0.01). The high cost of performing the medical treatment of approximately four hundred million baht per year. Seasonal variations demonstrated consistency with similar patterns during the cold and rainy seasons throughout the 5-year period. Regional distribution of the causative agent was also observed in Cholera, Typhoid, and Amoebiasis cases. A08: viral and other specified intestinal infections and A09: other gastroenteritis and colitis of infectious and unspecified origin were the two most common causes of diarrheal diseases. CONCLUSIONS: The incidence rate of acute diarrhea in Thai children under five years of age was higher while the mortality rate of acute diarrhea was lower than those in the past decade. A similar seasonal outbreak of acute diarrhea was seen during each examined year. The causative agent was not significant and was mainly unspecific. TRIAL REGISTRATION: Number TCTR20220117002, date of registration: 17/01/2022, site: Thai Clinical Trials Registry, URL http://www.thaiclinicaltrials.org/show/TCTR20220117002.

Treatment outcomes of high-dose chemotherapy plus stem cell rescue in high-risk neuroblastoma patients in Thailand.

BACKGROUND: In 2013, the Thai Pediatric Oncology Group (ThaiPOG) introduced a national protocol in which high-dose chemotherapy plus stem cell rescue is performed without immunotherapy. METHODS: This study aimed to elucidate the outcomes of high-risk neuroblastoma (HR-NB) patients treated with the ThaiPOG protocol. This retrospective cohort review included 48 patients (30 males, 18 females) with a median age of 3 years (range, 8 months to 18 years) who were treated at 5 ThaiPOG treatment centers in Thailand in 2000-2018. RESULTS: Eight of the 48 patients showed MYCN amplification. Twenty-three patients (48%) received 131I-meta-iodobenzylguanidine prior to high-dose chemotherapy and stem cell rescue. The majority of patients achieved a complete or very good response prior to consolidation treatment. The 5-year overall survival (OS) and event-free survival (EFS) rates were 45.1% and 40.4%, respectively. Patients aged >2 years had a nonsignificantly higher mortality risk (hazard ratio [HR], 2.66; 95% confidence interval [CI], 0.92-7.68; P=0.07). The MYCN amplification group had lower OS and EFS rates than the MYCN nonamplification group, but the difference was not statistically significant (45% OS and 37.5% EFS vs. 33.3% OS and 16.6% EFS; P=0.67 and P=0.67, respectively). Cis-retinoic acid treatment for 12 months was a strong prognostic factor that could reduce mortality rates among HR-NB patients (HR, 0.27; 95% CI, 0.09-0.785; P=0.01). CONCLUSION: High-dose chemotherapy plus stem cell rescue followed by cis-retinoic acid for 12 months was well tolerated and could improve the survival rates of patients with HR-NB.

NUDT15 is a key genetic factor for prediction of hematotoxicity in pediatric patients who received a standard low dosage regimen of 6-mercaptopurine.

6-Mercaptopurine (6-MP) is commonly used for treatment of acute lymphoblastic leukemia (ALL). The incidence of hematotoxicity caused by this drug is quite high in Asians even using a standard low dosage regimen. The present study was aimed to elucidate the impact of thiopurine S-methyltransferase (TPMT), a nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15), inosine triphosphatase (ITPA) and ATP Binding Cassette Subfamily C Member 4 (ABCC4) polymorphisms on hematotoxicity in pediatric patients who received a standard low starting dose of 6-MP. One hundred and sixty-nine pediatric patients were enrolled and their genotypes were determined. Patients who carried NUDT15∗3 and NUDT15∗2 genotypes were at a 10-15 fold higher risk of severe neutropenia than those of the wild-type during the early months of the maintenance phase. Risk of neutropenia was not significantly increased in patients with other NUDT15 variants as well as in patients with TPMT, ITPA or ABCC4 variants. These results suggest that NUDT15 polymorphisms particularly, NUDT15∗3 and NUDT15∗2, play major roles in 6-MP-induced severe hematotoxicity even when using a standard low dosage of 6-MP and genotyping of these variants is necessary in order to obtain precise tolerance doses and avoid severe hematotoxicity in pediatric patients.

Meta-Analysis of NUDT15 Genetic Polymorphism on Thiopurine-Induced Myelosuppression in Asian Populations.

Backgound: The high incidence of thiopurine-induced myelosuppression in Asians is known to be attributable to genetic variation in thiopurine metabolism. A quantitative synthesis to summarize the genetic association with thiopurine-induced myelosuppression in Asians was therefore conducted. Methods: A Literature search was performed from January 2016 to May 2021 in the following databases: PubMed, Web of Science, and Embase and addition search included the studies from Zhang et al. Two reviewers independently extracted the following data: the author's name, year of publication, ethnicity, drugs, diseases, genetic polymorphisms, onset, type of myelosuppression and results of Hardy-Weinberg equilibrium. The Newcastle-Ottawa Scale was used to assess the quality of the studies. The pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the associations of NUDT15 and the risk of thiopurine-induced myelosuppression stratified by onset and type of myelosuppressive. Subgroup analysis by NUDT15 genetic polymorphisms was performed. Results: A total of 30 studies was included in this meta-analysis. The overall OR for the relationship between NUDT15 genetic polymorphisms and thiopurine-induced early onset of leukopenia and neutropenia in Asian populations were 11.43 (95% CI 7.11-18.35) and 16.35 (95% CI 10.20-26.22). Among NUDT15 polymorphisms, NUDT15*3 showed a significantly increased risk of early leukopenia (OR 15.31; 95% CI 9.65-24.27) and early neutropenia (OR 15.85; 95% CI 8.80-28.53). A significantly higher thiopurine-induced early neutropenic risk was also found for NUDT15*2 (OR 37.51; 95% CI 1.99-708.69). Whereas, NUDT15*5 and NUDT15*6 variants showed a lower risk of leukopenia. Conclusion: This study suggests that NUDT15*3 and NUDT15*2 are important genetic markers of thiopurine-induced early onset of myelotoxicity in Asians, therefore, early detection of these variants before initiating thiopurine therapy is necessary.

Hand Hygiene Habits and Prevalence of Hand Eczema During the COVID-19 Pandemic.

PURPOSE: This study aimed to explore the prevalence of and possible risk factors for hand eczema with respect to the dissemination of information about new hand hygiene habits to protect against ongoing COVID-19 cross-transmission. The authors conducted a survey among health care workers (HCWs) and non-HCW populations in Khon Kaen, Thailand. RESULTS: A total of 805 participants participated. The prevalence of hand eczema in the study population was 20.87%. There were several risk factors, including working as a HCW, having a history of previous hand eczema, having underlying atopic dermatitis, wearing gloves in everyday life, and washing hands frequently (more than 10 times/day). Hand hygiene with alcohol-based products was shown to be a risk factor for hand eczema, (OR (95% CI) 1.86 (1.03-3.35), P = .04). CONCLUSION: In terms of hand eczema prevention, we suggest that the use of alcohol-based products should be discontinued if other handwashing methods are available. The following factors increase the risk of hand eczema: being a HCW, having previous hand eczema, and having underlying atopic dermatitis. Proper strategies in terms of hand eczema prevention should be addressed, especially in this group, since we need to continue performing hand hygiene during the ongoing COVID-19 pandemic.