Dengue virus transmission risk in blood donation: Evidence from Thailand.

Individuals infected with dengue virus (DENV) often show no symptoms, which raises the risk of DENV transfusion transmission (TT-DENV) in areas where the virus is prevalent. This study aimed to determine the evidence of DENV infection in blood donors from different geographic regions of Thailand. A cross-sectional study was conducted on blood donor samples collected from the Thai Red Cross National Blood Center and four regional blood centers between March and September 2020. Screening for DENV nonstructural protein 1 (NS1), anti-DENV immunoglobulin G (IgG), and IgM antibodies was performed on residual blood from 1053 donors using enzyme-linked immunosorbent assay kits. Positive NS1 and IgM samples indicating acute infection were verified using four different techniques, including quantitative real-time (q) RT-PCR, nested PCR, virus isolation in C6/36 cells, and mosquito amplification. DENV IgG seropositivity was identified in 89% (938/1053) of blood donors. Additionally, 0.4% (4/1053) and 2.1% (22/1053) of Thai blood donors tested positive for NS1 and IgM, respectively. The presence of asymptomatic dengue virus infection in healthy blood donors suggests a potential risk of transmission through blood transfusion, posing a concern for blood safety.

Proceedings of the 6th Asia Dengue Summit, June 2023.

The 6th Asia Dengue Summit (ADS) themed "Road Map to Zero Dengue Death" was held in Thailand from 15th-16th June 2023. The summit was hosted by Tropical Medicine Cluster, Chulalongkorn University, Bangkok, Thailand in conjunction with Queen Saovabha Memorial Institute, The Thai Red Cross Society; Faculty of Tropical Medicine, Mahidol University; and the Ministry of Public Health. The 6th ADS was convened by Asia Dengue Voice and Action (ADVA); Global Dengue and Aedes Transmitted Diseases Consortium (GDAC); Southeast Asian Ministers of Education Tropical Medicine and Public Health Network (SEAMEO TROPMED); Fondation Mérieux (FMx) and the International Society for Neglected Tropical Diseases (ISNTD). Dengue experts from academia and research, and representatives from the Ministries of Health, Regional and Global World Health Organization (WHO) and International Vaccine Institute (IVI) participated in the three-day summit. With more than 51 speakers and 451 delegates from over 24 countries, 10 symposiums, and 2 full days, the 6th ADS highlighted the growing threat of dengue and its antigenic evolution, flagged the urgent need to overcome vaccine hesitancy and misinformation crisis, and focused on dengue control policies, newer diagnostics, therapeutics and vaccines, travel-associated dengue, and strategies to improve community involvement.

The Surveillance of Acute Encephalitis Syndrome in Thailand, 2003-2019: A Perspective for Prevention and Control.

Background: Acute encephalitis syndrome (AES) is an infection of the central nervous system with high case-fatality rates. Japanese encephalitis virus (JEV) is the most common vaccine preventable cause of AES in Asia and part of the Western Pacific. In 2003, the JE vaccine was introduced into Thailand's National Immunization Program and expanded to all provinces. This study reviews data from the national surveillance system on the incidence of AES, including Japanese encephalitis in Thailand to guide surveillance, control, and prevention strategies. Materials and Methods: We collected data on all patients diagnosed with AES and reported to the Bureau of Epidemiology, Ministry of Public Health, Thailand, from 2003 to 2019. Results: A total of 9566 AES patients and 266 death cases were reported during these 17 years. Six hundred and forty-two (6.7%) patients were JE with 16 deaths. The incidence of AES increased from 0.47-0.51-1.36 cases per 100,000 population with a preponderance of cases in adults. CFR reduced from 6.25% - 6.94% in 2003-2005 to 0.78% in 2019. AES cases occurred all year round in all the age groups with a male predilection JE vaccination coverage had reached 83% by 2019. The patients were mainly from the north-eastern region of Thailand. Conclusion: Integrated surveillance regular monitoring, strengthening, and making immunization sustainable is required to improve and maintain progress toward JE control and prevention.

Seroprevalence of leptospirosis among blood donors in an endemic area.

Thailand is known to be endemic for leptospirosis. This bacterium may pose a potential risk to transfusion safety. This study was a cross-sectional study examining the seroprevalence of leptospirosis among Thai blood donors. A total of 1053 serum specimens collected from blood donors residing in 5 regions of Thailand during March to September 2020 were included in this study. All samples were tested for the presence of antibodies to 22 leptospiral serovars using the microscopic agglutination test (MAT) and anti-Leptospira IgG antibodies using commercially available enzyme immunoassay. We found no evidence of recent exposure to Leptospira spp. in sera of healthy Thai blood donors by MAT, including those in higher-risk areas. However, in this same group, we did find small numbers of past exposure (1.7%) to Leptospira spp. by IgG ELISA. According to the findings of this study, there is currently no evidence for implementing new blood banking procedures to identify possible carriers in Thailand, however these should be continually monitored and revised according to the infectious disease burden in each country. It should be noted that there was a difference in the occupation rate between the general population reported in Thailand and blood donors in this study; it may not reflect the actual situation in the country.

Efficacy of the combination of monoclonal antibodies against the SARS-CoV-2 Beta and Delta variants.

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the biggest healthcare issue worldwide. This study aimed to develop a monoclonal antibody against SARS-CoV-2 from B cells of recovered COVID-19 patients, which might have beneficial therapeutic purposes for COVID-19 patients. We successfully generated human monoclonal antibodies (hmAbs) against the receptor binding domain (RBD) protein of SARS-CoV-2 using developed hybridoma technology. The isolated hmAbs against the RBD protein (wild-type) showed high binding activity and neutralized the interaction between the RBD and the cellular receptor angiotensin-converting enzyme 2 (ACE2) protein. Epitope binning and crystallography results displayed target epitopes of these antibodies in distinct regions beneficial in the mix as a cocktail. The 3D2 binds to conserved epitopes among multi-variants. Pseudovirion-based neutralization results revealed that the antibody cocktail, 1D1 and 3D2, showed high potency in multiple variants of SARS-CoV-2 infection. In vivo studies showed the ability of the antibody cocktail treatment (intraperitoneal (i.p.) administration) to reduce viral load (Beta variant) in blood and various tissues. While the antibody cocktail treatment (intranasal (i.n.) administration) could not significantly reduce the viral load in nasal turbinate and lung tissue, it could reduce the viral load in blood, kidney, and brain tissue. These findings revealed that the efficacy of the antibody cocktail, 1D1 and 3D2, should be further studied in animal models in terms of timing of administration, optimal dose, and efficacy to mitigate inflammation in targeted tissue such as nasal turbinate and lung.

Proceedings of the 5th Asia Dengue Summit.

The 5th Asia Dengue Summit, themed "Roll Back Dengue", was held in Singapore from 13 to 15 June 2022. The summit was co-convened by Asia Dengue Voice and Action (ADVA), Global Dengue and Aedes transmitted Diseases Consortium (GDAC), Southeast Asian Ministers of Education Tropical Medicine and Public Health Network (SEAMEO TROPMED), and the Fondation Mérieux (FMx). Dengue experts from academia and research and representatives from the Ministries of Health, Regional and Global World Health Organization (WHO), and International Vaccine Institute (IVI) participated in the three-day summit. With more than 270 speakers and delegates from over 14 countries, 12 symposiums, and 3 full days, the 5th ADS highlighted the growing threat of dengue, shared innovations and strategies for successful dengue control, and emphasized the need for multi-sectoral collaboration to control dengue.

Serum Cortisol as a Biomarker of Severe Dengue.

Dengue infection presents a wide range of clinical symptoms. Serum cortisol is known as a severity predictor of serious infection but is not yet clearly understood in dengue infection. We aimed to investigate the pattern of cortisol response after dengue infection and evaluate the possibility of using serum cortisol as the biomarker to predict the severity of dengue infection. This prospective study was conducted in Thailand during 2018. Serum cortisol and other laboratory tests were collected at four time points: day 1 at hospital admission, day 3, day of defervescence (DFV) (4-7 days post-fever onset), and day of discharge (DC). The study recruited 265 patients (median age (IQR) 17 (13, 27.5)). Approximately 10% presented severe dengue infection. Serum cortisol levels were highest on the day of admission and day 3. The best cut-off value of serum cortisol level for predicting severe dengue was 18.2 mcg/dL with an AUC of 0.62 (95% CI, 0.51, 0.74). The sensitivity, specificity, PPV and NPV were 65.4, 62.3, 16 and 94%, respectively. When we combined serum cortisol with persistent vomiting and day of fever, the AUC increased to 0.76. In summary, serum cortisol at day of admission was likely to be associated with dengue severity. Further studies may focus on the possibility of using serum cortisol as one of the biomarkers for dengue severity.

Dengue amid COVID-19 pandemic.

The increasing in dengue cases nowadays is a global threat concern. Fifty per cent of the world's population is vulnerable to dengue infection with Asia contributing over two-thirds of the global burden. The double trouble of Coronavirus disease 2019 (COVID-19) arising from novel severe respiratory syndrome coronavirus (SARS-CoV-2) and dengue virus is a major challenge, particularly in developing countries due to overburdened public health systems and economic constraints including the ability to diagnose. The objective of this study was to analyze the prevalence of dengue in Thailand during the outbreak of COVID-19. We studied data on dengue cases reported at epidemiological information centers, the Bureau of Epidemiology, and the Ministry of Public Health, Thailand during 2019 to 2021. Patients can be observed across all age groups, particularly adolescents and adults. Dengue was seen year-round, with highest incidence in the rainy seasons between June and September. Total number of cases was markedly declined by nearly 93 percentage from 2019 to 2011. Taken together, Thailand is still at risk of spreading of dengue in the midst of COVID-19 pandemic. Continuous status updates on dengue patients in Thailand should be incorporated into global health advisory on preventive measures before travelling.

Epidemiology and costs of dengue in Thailand: A systematic literature review.

BACKGROUND: Dengue is the fastest-spreading vector-borne viral disease worldwide. In Thailand, dengue is endemic and is associated with a high socioeconomic burden. A systematic literature review was conducted to assess and describe the epidemiological and economic burden of dengue in Thailand. METHODS: Epidemiological and economic studies published in English and Thai between 2011-2019 and 2009-2019, respectively, were searched in MEDLINE, Embase, and Evidence-Based Medicines reviews databases. Reports published by the National Ministry of Public Health (MoPH) and other grey literature sources were also reviewed. Identified studies were screened according to predefined inclusion and exclusion criteria. Extracted data were descriptively summarised and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 155 publications were included in the review (39 journal articles and 116 grey literature). Overall, dengue incidence varied yearly, with the highest rates per 100,000 population in 2013 (dengue fever (DF) 136.6, dengue haemorrhagic fever (DHF) 100.9, dengue shock syndrome (DSS) 3.58) and 2015 (DF 133.1, DHF 87.4, DSS 2.14). Peak incidence coincided with the monsoon season, and annual mortality was highest for DSS, particularly in the age group 15-24-year-olds. The highest dengue incidence rates were reported in children (10-14-year-olds) and young adults (15-24-year-olds), irrespective of dengue case definition. Economic and societal burdens are extensive, with the average cost per case ranging from USD 41 to USD 261, total cost per year estimated at USD 440.3 million, and an average of 7.6 workdays lost for DHF and 6.6 days for DF. CONCLUSIONS: The epidemiological, economic, and societal burden of dengue in Thailand is high and underreported due to gaps in national surveillance data. The use of expansion factors (EFs) is recommended to understand the true incidence of dengue and cost-benefit of control measures. Furthermore, as dengue is often self-managed and underreported, lost school and workdays result in substantial underestimation of the true economic and societal burden of dengue. The implementation of integrated strategies, including vaccination, is critical to reduce the disease burden and may help alleviate health disparities and equity challenges posed by dengue.

Discovery and validation of circulating miRNAs for the clinical prognosis of severe dengue.

BACKGROUND: Early prognostic markers of severe dengue may improve case management and reduce dengue-related mortalities. This study aimed to identify circulating microRNAs (miRNAs) as biomarkers for predicting severe dengue. METHODOLOGY: Serum samples from dengue-infected patients were collected on the first day of admission. Patients were followed up for 14 days after admission to determine the final diagnosis. Participants were divided into non-severe and severe dengue, as defined by WHO 2009 criteria. Circulating microtranscriptome analysis was performed using NanoString miRNA Expression Assay. The expression level of candidate miRNAs were then validated by quantitative reverse transcription-PCR method. PRINCIPAL FINDINGS: The discovery cohort (N = 19) lead to the identification of 37 differentially expressed miRNAs between the two groups. Six up-regulated candidate miRNAs were selected and further validated in the larger cohort (N = 135). MiR574-5p and miR1246 displayed the highest diagnostic performance in discriminating between severe from non-severe dengue (ROC-AUC = 0.83). Additionally, miR574-5p and miR1246 had high sensitivity and high negative predictive value for detecting severe dengue. Multivariate analysis suggested that serum miR574-5p was an independent predictor of severe dengue (odds ratio 3.30, 95% CI 1.81-6.04; p<0.001). CONCLUSION: Our study indicated that circulating miRNAs, especially miR-574-5p and miR-1246, might be a promising diagnostic and prognostic biomarker for severe dengue upon hospital admission, especially when using these biomarkers on days 1 to 2 before the onset of severe dengue complications.

Invasive meningococcal disease in Malaysia, Philippines, Thailand, and Vietnam: An Asia-Pacific expert group perspective on current epidemiology and vaccination policies.

Invasive meningococcal disease (IMD) imposes a significant burden on the global community due to its high case fatality rate (4-20%) and the risk of long-term sequelae for one in five survivors. An expert group meeting was held to discuss the epidemiology of IMD and immunization policies in Malaysia, Philippines, Thailand, and Vietnam. Most of these countries do not include meningococcal immunization in their routine vaccination programs, except for high-risk groups such as immunocompromised people and pilgrims. It is difficult to estimate the epidemiology of IMD in the highly diverse Asia-Pacific region, but available evidence indicate serogroup B is increasingly dominant. Disease surveillance systems differ by country. IMD is not a notifiable disease in some of them. Without an adequate surveillance system in the region, the risk and the burden of IMD might well be underestimated. With the availability of new combined meningococcal vaccines and the World Health Organization roadmap to defeat bacterial meningitis by 2030, a better understanding of the epidemiology of IMD in the Asia-Pacific region is needed.

World Dengue Day: A call for action.

Commemorating the 2021 ASEAN Dengue Day and advocacy for World Dengue Day, the International Society for Neglected Tropical Diseases (ISNTD) and Asian Dengue Voice and Action (ADVA) Group jointly hosted the ISNTD-ADVA World Dengue Day Forum-Cross Sector Synergies in June 2021. The forum aimed to achieve international and multisectoral coordination to consolidate global dengue control and prevention efforts, share best practices and resources, and improve global preparedness. The forum featured experts around the world who shared their insight, research experience, and strategies to tackle the growing threat of dengue. Over 2,000 healthcare care professionals, researchers, epidemiologists, and policy makers from 59 countries attended the forum, highlighting the urgency for integrated, multisectoral collaboration between health, environment, education, and policy to continue the march against dengue. Sustained vector control, environmental management, surveillance improved case management, continuous vaccine advocacy and research, capacity building, political commitment, and community engagement are crucial components of dengue control. A coordinated strategy based on science, transparency, timely and credible communication, and understanding of human behavior is needed to overcome vaccine hesitancy, a major health risk further magnified by the COVID-19 pandemic. The forum announced a strong call to action to establish World Dengue Day to improve global awareness, share best practices, and prioritize preparedness in the fight against dengue.

Pertussis in Asia: Recent country-specific data and recommendations.

The Global Pertussis Initiative (GPI) Roundtable Meeting held in 2019, which preceded the COVID-19 pandemic, focused on the incidence, surveillance, and immunization practices for pertussis in the Asian region. Participants from China, India, Indonesia, Malaysia, Pakistan, Philippines, South Korea, Taiwan, and Thailand presented country-specific information on pertussis prevalence, diagnosis, surveillance, vaccine administration and schedules, maternal and neonatal disease rates, and policies and practice of vaccination during pregnancy. In recent years, many Asian countries have seen an increase in pertussis cases, although underreporting of the disease is a concern. Currently, most Asian countries have only passive surveillance for pertussis in place. There is a need for improved surveillance to determine the disease burden and justify vaccination policies and recommendations, such as essential vaccination, boosters, and vaccination during pregnancy. Better awareness of the disease in adolescents and adults is necessary, and infant and childhood vaccination schedules need to be improved in many countries. Differences between private versus public sector vaccination schedules and between whole-cell and acellular pertussis vaccines should continue to be examined. It can be anticipated that unmet needs in the prevention and management of pertussis will continue as the COVID-19 pandemic evolves and that key recommendations highlighted in this meeting report will be of ongoing importance.

Dengue pre-vaccination screening test evaluation for the use of dengue vaccine in an endemic area.

BACKGROUND: The dengue vaccine (Dengvaxia) is only recommended for individuals with prior dengue infection (PDI). This study aimed to perform a serosurvey to inform decision-making for vaccine introduction and identify appropriate target populations. We also evaluated the performance of the serological tests using plaque reduction neutralization test (PRNT) as a reference test in identifying PDI to determine suitability for pre-vaccination screening. METHODS: We enrolled 115 healthy individuals between 10 and 22 years of age living in the Ratchaburi province of Thailand. The serum samples were tested by PRNT to measure the prevalence and concentration of serotype-specific neutralizing antibodies. The performance of the IgG rapid diagnostic test (RDT, SD Bioline, Korea) and IgG enzyme-linked immunosorbent assay (ELISA, EUROIMMUN, Germany) in identifying PDI were evaluated by using PRNT as a reference method. RESULTS: Ninety-four (81.7%) individuals neutralized one or more dengue serotypes at a titer threshold greater than or equal to 10. Multitypic profiles were observed in 70.4% of the samples which increased to 91.9% in subjects aged 19-22. Among monotypic samples, the highest proportion was reactive against DENV-1 followed by DENV-2, DENV-3, and DENV-4. The highest anti-dengue antibody titers were recorded against DENV-1 and increased with age to a geometric mean NT50 titer (GMT) of 188.6 in the 19-22 age group. While both RDT and ELISA exhibited 100% specificity, RDT demonstrated low sensitivity (35%) with ELISA displaying much greater sensitivity (87%). CONCLUSIONS: Almost 80% of adolescents and youth in Ratchaburi province had already been exposed to one or more of the dengue virus serotypes. The dengue IgG RDT displayed low sensitivity and is likely not be suitable for dengue pre-vaccination screening. These results support the use of IgG ELISA test for dengue vaccination in endemic areas.

The burden of norovirus disease in children: a multi-country study in Chile, Brazil, Thailand and the Philippines.

BACKGROUND: Noroviruses (NoVs) cause acute gastroenteritis (AGE) worldwide, affecting children in particular. We aimed to estimate the burden of disease due to NoV among children aged <6 years in Brazil, Chile, Philippines and Thailand. METHODS: This was a prospective, hospital-based, observational study. Children were recruited over one year between 2014 and 2017. Four cohorts were analysed: community-acquired AGE outpatients and inpatients, nosocomial AGE inpatients, and asymptomatic outpatients. We collected demographic and clinical data, and a stool sample that was tested for NoV. Positive samples were tested for Rotavirus (RV) and NoV-genotyped. Disease severity was assessed by the Vesikari and modified Vesikari scores. Prevalence and incidence of NoV-AGE were estimated by cohort and country. RESULTS: 1637 participants yielded valid laboratory results. The proportion of NoV-positive cases was 23.8% (95% CI 20.8-27.2) in the outpatient cohort, 17.9% (15.0-21.3) in the hospital cohort, 21.4% (12.7-33.8) in the nosocomial cohort and 9.6% (6.9-13.2) in the asymptomatic cohort. Genotype GII.4 was predominant (58%). Less than 4% samples had RV coinfection. In general, NoV-positive subjects had more severe presentations than NoV-negative subjects. CONCLUSIONS: NoV caused AGE with substantial burden throughout the studied settings, with higher relative frequency in Brazil where RV vaccination coverage is high.

Endotoxemia and circulating bacteriome in severe COVID-19 patients.

BACKGROUND: When severe, COVID-19 shares many clinical features with bacterial sepsis. Yet, secondary bacterial infection is uncommon. However, as epithelium is injured and barrier function is lost, bacterial products entering the circulation might contribute to the pathophysiology of COVID-19. METHODS: We studied 19 adults, severely ill patients with COVID-19 infection, who were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 13th March and 17th April 2020. Blood samples on days 1, 3, and 7 of enrollment were analyzed for endotoxin activity assay (EAA), (1 → 3)-ß-D-glucan (BG), and 16S rRNA gene sequencing to determine the circulating bacteriome. RESULTS: Of the 19 patients, 13 were in intensive care and 10 patients received mechanical ventilation. We found 8 patients with high EAA (≥ 0.6) and about half of the patients had high serum BG levels which tended to be higher in later in the illness. Although only 1 patient had a positive blood culture, 18 of 19 patients were positive for 16S rRNA gene amplification. Proteobacteria was the most abundant phylum. The diversity of bacterial genera was decreased overtime. CONCLUSIONS: Bacterial DNA and toxins were discovered in virtually all severely ill COVID-19 pneumonia patients. This raises a previously unrecognized concern for significant contribution of bacterial products in the pathogenesis of this disease.

Meningococcal disease surveillance in the Asia-Pacific region (2020): The global meningococcal initiative.

The degree of surveillance data and control strategies for invasive meningococcal disease (IMD) varies across the Asia-Pacific region. IMD cases are often reported throughout the region, but the disease is not notifiable in some countries, including Myanmar, Bangladesh and Malaysia. Although there remains a paucity of data from many countries, specific nations have introduced additional surveillance measures. The incidence of IMD is low and similar across the represented countries (<0.2 cases per 100,000 persons per year), with the predominant serogroups of Neisseria meningitidis being B, W and Y, although serogroups A and X are present in some areas. Resistance to ciprofloxacin is also of concern, with the close monitoring of antibiotic-resistant clonal complexes (e.g., cc4821) being a priority. Meningococcal vaccination is only included in a few National Immunization Programs, but is recommended for high-risk groups, including travellers (such as pilgrims) and people with complement deficiencies or human immunodeficiency virus (HIV). Both polysaccharide and conjugate vaccines form part of recommendations. However, cost and misconceptions remain limiting factors in vaccine uptake, despite conjugate vaccines preventing the acquisition of carriage.

Pertussis vaccination in mixed markets: Recommendations from the Global Pertussis Initiative.

The Global Pertussis Initiative is an expert scientific forum that publishes consensus recommendations concerning pertussis for many regions of the world. Here, we give recommendations for the primary vaccination of infants in those countries where whole-cell pertussis (wP)- and acellular pertussis (aP)-containing combination vaccines are used in parallel. A selective literature review was performed concerning the influence on safety, immunogenicity, and effectiveness of mixing wP- and aP-containing vaccines for primary immunization of infants. In addition, local data were collected from various countries and the results discussed in a face-to-face meeting. Very few data addressing issues of mixing combination vaccines were identified, and no data were available concerning the effectiveness or duration of protection. It was also found that pharmacovigilance data are scarce or lacking in those countries where they would be needed the most. We then identified frequent problems occurring in low- and middle-income countries (LMICs) where both vaccine types are used. Relying on local knowledge, we give practical recommendations for a variety of situations in different settings. Specific needs for additional data addressing these issues were also identified. International bodies, such as the World Health Organization (WHO), as well as vaccine producers should try to find ways to highlight the problems of mixing wP- and aP-containing combination vaccines with robust data. Countries are urged to improve on their pharmacovigilance for vaccines. For practicing physicians, our recommendations offer guidance when wP- and aP-containing vaccines are used in parallel during primary immunization.