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The recombinant, live, attenuated, tetravalent dengue vaccine CYD-TDV has shown efficacy against all four dengue serotypes. In this exploratory study (CYD59, NCT02827162), we evaluated potential associations of host human leukocyte antigen (HLA) alleles with dengue antibody responses, CYD-TDV vaccine efficacy, and virologically-confirmed dengue (VCD) cases. Children 4-11 years old, who previously completed a phase 2b efficacy study of CYD-TDV in a single center in Thailand, were included in the study. Genotyping of HLA class I and II loci was performed by next-generation sequencing from DNA obtained from 335 saliva samples. Dengue neutralizing antibody titers (NAb) were assessed as a correlate of risk and protection. Regression analyses were used to assess associations between HLA alleles and NAb responses, vaccine efficacy, and dengue outcomes. Month 13 NAb log geometric mean titers (GMTs) were associated with decreased risk of VCD. In the vaccine group, HLA-DRB1*11 was significantly associated with higher NAb log GMT levels (beta: 0.76; p = 0.002, q = 0.13). Additionally, in the absence of vaccination, HLA associations were observed between the presence of DPB1*03:01 and increased NAb log GMT levels (beta: 1.24; p = 0.005, q = 0.17), and between DPB1*05:01 and reduced NAb log GMT levels (beta: -1.1; p = 0.001, q = 0.07). This study suggests associations of HLA alleles with NAb titers in the context of dengue outcomes. This study was registered with clinicaltrials.gov: NCT02827162.

Most cases of dengue virus infection are mild, but severe cases can be fatal. Therefore, identification of factors associated with dengue severity is essential to improve patient outcomes and reduce mortality. The objective of this study was to assess associations between nutritional status and dengue severity among Thai children and adolescents. This retrospective cross-sectional study was based on the medical records of 355 patients with dengue treated at the Hospital for Tropical Disease (Bangkok, Thailand) from 2017 to 2019. Subjects were Thai children aged less than 18 years with dengue virus infection confirmed by positive NS1 antigen or IgM. The 1997 and 2009 World Health Organization (WHO) dengue classifications were used to define disease severity and body mass index for age while the WHO growth chart was used to classify nutritional status. The proportions of patients with dengue fever who were underweight, normal weight, and overweight were 8.8%, 61.5%, and 29.7%, respectively. The proportions of patients with dengue haemorrhagic fever (DHF) who were underweight, normal weight, and overweight were 10.2%, 66.1%, and 23.7%, respectively. The proportions of patients with non-severe dengue who were underweight, normal weight, and overweight were 8.6%, 60.9%, and 30.5%, respectively; the same proportions of patients with severe dengue were 10.5%, 67.1%, and 22.4%, respectively. Higher proportions of patients with severe plasma leakage (DHF grade III and IV) were overweight compared with those with mild plasma leakage (DHF grade I and II) (45.5% vs. 18.8%). No difference in nutritional status was observed in patients with different dengue severity.

Background Undernutrition has been shown to be associated with various infectious diseases. However, the recent improvement in nutritional status and management for infectious diseases worldwide necessitates the re-evaluation of this association. Methods A retrospective study was conducted in children aged Results Most of the patients had mild disease and most of the undernourishment was mild. The prevalence of underweight in dengue, malaria and acute diarrhea was 24.0%, 34.7% and 38.7%, respectively, and the prevalence of low height for age was 12.0%, 36.0% and 36.0%, respectively. Malaria and acute diarrhea were associated with underweight but not low height for age. Dengue was neither associated with underweight nor low height for age. Conclusion Although there has been an improvement in nutritional status and health care facilities, underweight has been still prevalent in rural areas and associated with malaria and acute diarrhea. Implication The surveillance for nutritional status should be continuously performed particularly in children with some diseases, e.g. malaria and acute diarrhea, and additional food supplementation should be provided.

Background Dengue is a major public health problem in Thailand, but data are often focused on certain dengue-endemic areas. Methods: To better understand dengue epidemiology and clinical characteristics in Thailand, a fever surveillance study was conducted among patients aged 1–55 years, who presented with non-localized febrile illness at Bang Phae Community Hospital in Ratchaburi province, Thailand from October 2011 to September 2016. Results Among 951 febrile episodes, 130 were dengue-confirmed. Individuals aged 10–14 years were mostly affected, followed by those 15–19 years-of-age, with about 15% of dengue-confirmed cases from adults 25 years and older. There were annual peaks of dengue occurrence between June-November. Most prevalent serotype in circulation was DENV-2 in 2012, DENV-3 in 2014, and DENV-4 & -3 in 2015. Among dengue cases, 65% were accurately detected using the dengue NS1 RDT. Detection rate was similar between secondary and primary dengue cases where 66% of secondary vs. 60% of primary dengue cases had positive results on the NS1 RDT. Among dengue cases, 66% were clinically diagnosed with suspected dengue or DHF, prior to lab confirmation. Dengue was positively associated with rash, headache, hematemesis and alterations to consciousness, when compared to non-dengue. Dengue patients were 10.6 times more likely to be hospitalized, compared to non-dengue cases. Among dengue cases, 95 were secondary and 35 were primary infections. There were 8 suspected DHF cases and all were identified to be secondary dengue. Secondary dengue cases were 3.5 times more likely to be hospitalized compared to primary dengue cases. Although the majority of our dengue-positive patients were secondary dengue cases, with few patients showing manifestations of DHF, our dengue cases were mostly mild disease. Even among children < 10 years-of-age, 61% had secondary infection and the rate of secondary infection increased with age. Conclusion While the majority of dengue-confirmed cases were children, almost three-quarters of dengue-confirmed cases in this study were secondary dengue. Our study results consistent with previous data from the country confirm the hyperendemic transmission of DENV in Thailand, even in the non-epidemic years. With various interventions becoming available for dengue prevention and control, including dengue vaccines, decision-making on future implementation strategies should be based on such burden of disease data., Author summary Dengue is a well-known public health problem in Thailand. To identify epidemiologic and clinical patterns of dengue in Thailand, we studied 951 febrile patients with fever, aged 1–55 years, who attended Bang Phae district hospital in Ratchaburi province, Thailand. Patients were tested with a rapid test for dengue, and further tests were carried out on paired blood samples taken 10–21 days apart. Overall, 14% of the febrile episodes identified between October 2011 and September 2016 were dengue-confirmed. Teenagers were mostly affected with only few adults. Dengue peaks occurred between June-November, but there was no large epidemic during the study period. DENV type 2 was the main serotype in circulation in 2012, DENV type 3 in 2014, and DENV types 4 and 3 in 2015. Dengue cases were 11 times more likely to be hospitalized than non-dengue cases. Dengue patients were more likely to present with rash, headache, hematemesis and alterations to consciousness, compared to non-dengue. Two thirds of the dengue cases were clinically diagnosed with suspected dengue or DHF, even without lab confirmation. Secondary dengue cases were about three times more common than primary cases. Even among children < 10 years-of-age, 61% of the patients were of secondary infection. Among dengue cases, 65% were accurately detected using the dengue RDT. This was not different between secondary and primary dengue cases. All 8 patients clinically diagnosed with DHF were secondary dengue cases. Although most of our dengue-positive patients were secondary dengue cases, we only observed few patients showing DHF. Thus, we concluded that our dengue cases were mostly of mild dengue illness. Our study results support the previous data confirming the high burden of dengue in Thailand and such information would help to make decisions on future implementation of various tools for dengue prevention and control.

Hand, foot, and mouth disease (HFMD) is a contagious childhood illness and annually affects millions of children aged less than 5 years across the Asia–Pacific region. HFMD transmission mainly occurs through direct contact (person-to-person) and indirect contact with contaminated surfaces and objects. Therefore, public health measures to reduce the spread of HFMD in kindergartens and daycare centers are essential. Based on the guidelines by the Department of Disease Control, a school closure policy for HFMD outbreaks wherein every school in Thailand must close when several HFMD classrooms (more than two cases in each classroom) are encountered within a week, was implemented, although without strong supporting evidence. We therefore conducted a prospective cohort study of children attending five kindergartens during 2019 and 2020. We used molecular genetic techniques to investigate the characteristics of the spreading patterns of HFMD in a school-based setting in Bangkok, Thailand. These analyses identified 22 index cases of HFMD (symptomatic infections) and 25 cases of enterovirus-positive asymptomatic contacts (24 students and one teacher). Enterovirus (EV) A71 was the most common enterovirus detected, and most of the infected persons (8/12) developed symptoms. Other enteroviruses included coxsackieviruses (CVs) A4, CV-A6, CV-A9, and CV-A10 as well as echovirus. The pattern of the spread of HFMD showed that 45% of the subsequent enteroviruses detected in each outbreak possessed the same serotype as the first index case. Moreover, we found a phylogenetic relationship among enteroviruses detected among contact and index cases in the same kindergarten. These findings confirm the benefit of molecular genetic assays to acquire accurate data to support school closure policies designed to control HFMD infections.

The 1st Workshop on National Immunization Programs and Vaccine Coverage in Association of Southeast Asian Nations (ASEAN) Countries Group (WNIPVC-ASEAN) held a meeting on April 30, 2015, Pattaya, Thailand under the auspices of the Pediatric Infectious Diseases Society and the World Health Organization (WHO). Reports on the current status and initiatives of the national immunization program (NIP) in each ASEAN countries that attended were presented. These reports along with survey data collected from ministries of health in ASEAN countries NIPs demonstrate that good progress has been made toward the goal of the Global Vaccine Action Plan (GVAP). However, some ASEAN countries have fragile health care systems that still have insufficient vaccine coverage of some basic EPI antigens. Most ASEAN countries still do not have national coverage of some new and underused vaccines, and raising funds for the expansion of NIPs is challenging. Also, there is insufficient research into disease burden of vaccine preventable diseases and surveillance. Health care workers must advocate NIPs to government policy makers and other stakeholders as well as improve research and surveillance to achieve the goals of the GVAP.

Background: Streptococcus pneumoniae, an important pathogen worldwide, causes a wide range of diseases mostly in young children and older adults. The heptavalent pneumococcal conjugate vaccine (PCV7) that is composed of seven serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F), was most prevalent in Thailand during this vaccination study. Aim: To determine immune responses to PCV7 among Thai children with high risk for invasive pneumococcal disease and whether children had specific antibody responses to related serotype 19A. Methods: The antibody-mediated opsonophagocytic killing assay (OPKA) was employed to detect the humoral immune response. One hundred and twenty-nine children (72 males and 57 females) were enrolled and divided into three groups according to age and vaccine dosages received: >12 months and received two vaccine doses, 7-12 months and received three vaccine doses, and 2-6 months and received four vaccine doses. These groups were then categorised into five groups based on disease: congenital heart disease, prematurity, chronic lung disease, haematological disease, and HIV. Serotype-specific antibody responses from children in all disease groups were comparatively analysed. Results: Low antibody responses to serotypes 9V and 23F, moderate responsive antibody titres to serotypes 4, 18C, 19A, and 19F, and high antibody responses to serotypes 6B and 14 were observed. Conclusion: These results suggest that children at high risk of invasive pneumococcal disease could develop functional antibody responses to some vaccine serotypes after PCV7 vaccination.

Summary: Inactivated mouse-brain-derived Japanese encephalitis vaccine has a worrisome safety profile and the live attenuated vaccine is unsuitable in immunodeficiency. This study aimed to evaluate the immunogenicity and safety of an inactivated chromatographically purified Vero-cell-derived JE vaccine (CVI-JE, Beijing P-3 strain) in children. 152 healthy Thai children, with an average (SD) age of 14.4 (3.8) months, received 3 doses of CVI-JE on days 0, 7–28, and one year. Homologous JE neutralizing antibody titers (NT) were measured. All subjects had seroprotection [geometric mean titer (GMT) 150] 28 days' post 2nd vaccination. The seroprotection rates at 1 year after primary series and and 1 month after the booster were 89.3% (GMT 49) and 100% (GMT 621), respectively. Local and systemic reactions–fever (17.6%), vomiting (8%), and poor appetite (5.3%)–were noted within 28 days' post-vaccination. All these symptoms were self-limited. Conclusions: CVI-JE is safe, immunogenic, and provided high NT.

The seroprevalence of toxoplasma antibodies in pregnant women and the prevalence of congenital infection differ widely between countries. A few cases of congenital toxoplasmosis diagnosed after the neonatal period, with long-term sequelae, have been reported in Thailand. No data on the prevalence of congenital toxoplasmosis have been documented and no screening for toxoplasmosis during pregnancy has been undertaken in Thailand.A questionnaire enquiring about cases of congenital toxoplasmosis during 1995-2013 was distributed to paediatricians in referral and university hospitals in Thailand and the responses were analysed. Specific toxoplasma IgM antibody and clinical features were used for diagnosis.There were 20 cases - 13 most likely and seven suspected cases of congenital toxoplasmosis. Most patients had systemic manifestations, but only 25% of diagnosed patients exhibited the classic triad of hydrocephalus, cerebral calcification and chorioretinitis. One of the five deceased patients lived beyond the age of 13 years and died of a pulmonary infection. All 15 surviving cases developed deafness, visual impairment or developmental delay.Twenty cases of congenital toxoplasmosis are reported. Delayed diagnosis and treatment resulted in a poor outcome. The prevention of toxoplasmosis in pregnant women and prompt diagnosis and appropriate treatment of congenital toxoplasmosis should be a priority in order to prevent a poor outcome in infected children.

Objective: To investigate the long-term safety of a tetravalent dengue vaccine (CYD-TDV) in children in a phase Π b follow-up study in Thailand. Methods: In the phase Π b study, children aged 4-11 years were randomized (2:1) to receive three injections of CYD-TDV or serve as control at 6-month intervals, with 25 months’ active follow-up (active phase). This study was an additional four-year passive surveillance for hospitalized virologically-confirmed dengue (VCD; hospital phase). Cases of hospitalized VCD, severe hospitalized VCD, vaccine-related serious adverse events, and deaths were reported for the total population, with post-hoc analyses by enrollment age (

This retrospective descriptive study was conducted at Queen Sirikit National Institute of Child Health (QSNICH), Bangkok, Thailand to describe the clinical features of gastrointestinal salmonellosis in children. The medical records of 134 patients admitted to QSNICH in 2009 who had a positive stool culture for Salmonella spp were reviewed. Demographic, clinical, laboratory, treatment, culture and antimicrobial sensitivity data were collected and analyzed. The mean age of the patients was 22.9 months (range 0.5 to 158 months); 76.9% were2 years old. The male to female ratio was 1.5:1. Salmonella B was most commonly found serogroup (47%). The common clinical manifestations included diarrhea (99.3%), fever (93.3%), dehydration (64.9%) and nausea/vomiting (48.5%). Most of the Salmonella isolates were sensitive to a fluoroquinolone and many were sensitive to Cotrimoxazole, but few were sensitive to ampicillin. There were no significant differences in the clinical manifestations and drug sensitivities of the different Salmonella serogroups, except convulsions were more common in Salmonella E infected patients (p = 0.04) and more Salmonella C isolates were sensitive to ampicillin (p = 0.04). There was no significant correlation between clinical course and antimicrobial treatment, except the duration of diarrhea was significantly longer in patients who received antimicrobial treatment (mean 6.1, SD 4.7 days vs mean 4.2, SD 2.1 days) (p = 0.03). Three patients had Salmonella bacteremia. Three patients died but not directly due to Salmonella infection.

This study assessed clinical differences between invasive pneumococcal disease (IPD) caused by penicillin-resistant and penicillin-sensitive Streptococcus pneumoniae.Patients with IPD confirmed during January 1996-December 2007 at three hospitals were included. Clinical characteristics and outcomes were compared between patients infected with penicillin-resistant Streptococcus pneumoniae (PRSP) and penicillin-sensitive Streptococcus pneumoniae (PSSP).Sixty-nine patients with IPD were identified during the study period, 20 (29%) of whom were infected with PRSP and 49 (71%) with PSSP. Sex, mean age, underlying diseases and seasonal variation did not differ statistically between the two groups. No significant differences were identified in clinical course as measured by time until defervescence, duration of hospitalization and clinical outcome. Minimum inhibitory concentrations (MIC) for other antibiotics were determined; 20% and 10% of PRSP isolates were nonsusceptible to cephalosporins and meropenem, respectively, but all isolates were sensitive to vancomycin.There were no significant differences identified in the clinical epidemiology of lPD cases caused by PRSP and PSSP.

Background The WHO ‘Global Strategy for Dengue Prevention and Control, 2012–2020’ addresses the growing need for the treatment of dengue, and targets a 25% reduction in morbidity and 50% in mortality (using 2010 estimates as baseline). Achieving these goals requires future dengue prevention strategies that will employ both potential vaccines and sustainable vector-control measures. Maternally transferred dengue antibody is an important factor in determining the optimal age for dengue vaccination. Objectives To estimate the seroprevalence of dengue antibodies among mothers living in an area of high endemicity – Ban Pong, Ratchaburi Province – and to assess maternal dengue antibodies transferred to cord blood. Materials & Methods A cross-sectional study was conducted with 141 pregnant women who delivered at Ban Pong Hospital, Ratchaburi, Thailand. Maternal-cord paired sera were tested for dengue neutralizing (NT) antibody by PRNT50 assay. A ratio of ≥ 1:10 NT titer to dengue serotype was considered seropositive. Results Most mothers (137/141, 97.2%) had NT antibodies to at least one dengue serotype in their sera. At birth, the proportion of cord sera with NT antibodies to DEN-1, DEN-2, DEN-3, and DEN-4, were high and similar to the sera of their mothers, at 93.6%, 97.2%, 97.9%, and 92.2%, respectively. The dengue geometric mean titers (GMT) in cord blood were significantly higher than the maternal antibodies (p, Author Summary Dengue is the fastest spreading mosquito-borne viral infection. Infections cause mild to severe diseases, including dengue hemorrhagic fever (DHF), a severe form that may kill infants and young children. Dengue virus antibody transfer from mother to fetus in pregnancy confers protection at birth, thereafter subsiding to a lower level that may cause DHF in infants. Infant dengue antibodies levels also influence the optimal age for dengue vaccination because of neutralization of the proposed live virus vaccine by the protective antibody levels in the newborn. To establish the optimal age, we identified mother-child pairs in which maternal dengue antibodies were transferred from mother to fetus in this study. Then a follow-up study would measure the infant antibody levels. Our study found that 97.2% of pregnant women giving birth in a dengue-endemic area had evidence of previous dengue infection. All umbilical cord blood from fetuses had the same proportion of positive tests for the presence of dengue antibodies, but had a higher dengue antibody levels compared to their mothers. The period of protection provided by maternally transferred dengue antibodies might affect the disease burden among infants and offer a better understanding of the optimal age for dengue vaccination.