Association between nutritional status and dengue severity in Thai children and adolescents.

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.

Antibody persistence upto 5 years after primary immunization and booster with an inactivated chromatographically purified Vero cell-derived Japanese encephalitis vaccine in Thai children.

Japanese encephalitis is the main cause of viral encephalitis in Asia. In a previous single-arm vaccine trial, an inactivated chromatographically purified Japanese encephalitis Vero cell vaccine (CVI-JE; JEVACTM) was safe and immunogenic in 152 Thai children aged 1-3 years receiving a 2-dose primary immunization and booster dose 1 year later. We conducted a 5-year follow-up assessment of the persistence of the immune response the 144 children remaining in this cohort after first booster dose. Immunity was assessed by 50% plaque reduction neutralization test annually for up to 5 years post-booster. Seroprotection rates (95%CI) decreased from 100% (97.1-100) at 1 year post-booster to 93% (85.0-98.3) at 5 years post-booster. No serious vaccine-related adverse events or Japanese encephalitis infections were reported. A 2-dose primary immunization and booster 1 year later with CVI-JE provided long-lasting immunity in the majority of children.

Association of undernutrition with dengue, malaria and acute diarrhea among children in a Thai-Myanmar border.

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 <14 years old with dengue, malaria or acute diarrhea who visited or were admitted to Tha Song Yang hospital, near the Thai-Myanmar border. 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.

Associations of human leukocyte antigen with neutralizing antibody titers in a tetravalent dengue vaccine phase 2 efficacy trial in Thailand.

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.

Clinical and epidemiologic characteristics associated with dengue fever in 2011-2016 in Bang Phae district, Ratchaburi province, Thailand.

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.

Molecular Epidemiological Study of Hand, Foot, and Mouth Disease in a Kindergarten-Based Setting in Bangkok, Thailand.

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.

Evaluation of Immunization Services for Children of Migrant Workers Along Thailand-Myanmar Border: Compliance with Global Vaccine Action Plan (2011-2020).

Immunization is a core component of the human right to health. However, accessibility to the Expanded Program on Immunization (EPI) might be difficult among migrant children. This study aims to assess the vaccination coverage of migrant children under a mobile immunization program, initiated by the Thai government in 2014. A cross-sectional, mixed-methods study was conducted in five districts along the Thailand-Myanmar border during July-December 2018. The immunization history during their first year of life was obtained. Focus group discussions were conducted among stakeholders to explore their satisfaction toward the immunization service. Mothers/guardians of 1707 migrant children participated in the survey, with a 71% response rate. The vaccination coverage increased during 2014-2017. The highest vaccination coverage was observed for Bacillus CalmetteGuérin vaccine, with 83.2% coverage in 2017. The vaccination coverage of three doses of diphtheriatetanuspertussis vaccine and Hepatitis B vaccine and oral polio vaccine increased from 34.8% in 2014 to 56.3% in 2017. For measles-containing vaccine, the vaccination coverage increased from 32.4% in 2014 to 54.6% in 2017. Overall, all stakeholders were satisfied with the immunization service. Increased workload and communication barriers were the main factors that influenced the satisfaction toward the immunization program.

Immunogenicity and safety of inactivated chromatographically purified Vero cell-derived Japanese encephalitis vaccine in Thai children.

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.

Report on: "The 1st Workshop on National Immunization Programs and Vaccine Coverage in ASEAN Countries, April 30, 2015, Pattaya, Thailand".

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.

Neutralizing dengue antibody in pregnant Thai women and cord blood.

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<0.001): highest in DEN-2, followed by DEN-3, and then DEN-1. The GMT of DEN-4 was the lowest among all four serotypes. CONCLUSIONS: Dengue infection is highly prevalent among pregnant women in this dengue-endemic area. Most of the cord blood had transferred dengue antibodies, which may have an impact on the disease burden in this population.

Congenital toxoplasmosis: an uncommon disease in Thailand.

BACKGROUND: 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. SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Clinical features of gastrointestinal salmonellosis in children in Bangkok, Thailand.

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% were < 2 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.

Frequency and clinical course of invasive pneumococcal disease caused by penicillin-resistant and penicillin-sensitive Streptococcus pneumoniae in Thai children.

OBJECTIVE: This study assessed clinical differences between invasive pneumococcal disease (IPD) caused by penicillin-resistant and penicillin-sensitive Streptococcus pneumoniae. MATERIAL AND METHOD: 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). RESULTS: 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. CONCLUSION: There were no significant differences identified in the clinical epidemiology of lPD cases caused by PRSP and PSSP.