Relative vaccine effectiveness of ChAdOx1/AZD1222 vaccines as booster dose via intradermal injection with a one-fifth dose compared with the intramuscular injection in the prevention of SAR-CoV-2 infections in Phuket - A Retrospective Cohort Study.

OBJECTIVES: This study assessed the real-world relative vaccine effectiveness of the ChAdOx1/AZD1222 vaccine given intradermally at one-fifth dose compared to the standard intramuscular injection, following the completion of two doses of CoronaVac, due to limited vaccine availability in Thailand during the Coronavirus disease 2019 (COVID-19) pandemic. METHOD: This retrospective cohort study used 138,264 records from Vachira Phuket Hospital, Phuket, Thailand. The records were divided into two groups: 49,387 recipients received one-fifth doses via intradermal injections, and 88,877 recipients received standard-dose intramuscular injections from September 14 to October 3, 2021, with follow-up until December 31, 2021. Relative vaccine effectiveness for the cohorts was estimated using Cox regression, adjusting for demographic and clinical risk factors. RESULTS: The adjusted hazard ratio between the intradermal and intramuscular groups was 0.88 (95% Confidence Interval 0.76-1.02, p = 0.09), indicating a non-significant protective factor for the intradermal group. Further stratified analysis revealed no significant difference between the two groups. The 21 and 28-day post-vaccination periods minimized the possibility of confounding due to differences in the cohorts' timeframes. CONCLUSION: A booster dose of ChAdOx1/AZD1222 given intradermally at one-fifth dose did not show a significant difference compared to the standard intramuscular injection.

Automating the Generation of Notifiable Bacterial Disease Reports: Proof-of-Concept Study and Implementation in Six Hospitals in Thailand.

Information on notifiable bacterial diseases (NBD) in low- and middle-income countries (LMICs) is frequently incomplete. We developed the AutoMated tool for the Antimicrobial resistance Surveillance System plus (AMASSplus), which can support hospitals to analyze their microbiology and hospital data files automatically (in CSV or Excel format) and promptly generate antimicrobial resistance surveillance and NBD reports (in PDF and CSV formats). The NBD reports included the total number of cases and deaths after Brucella spp., Burkholderia pseudomallei, Corynebacterium diphtheriae, Neisseria gonorrhoeae, Neisseria meningitidis, nontyphoidal Salmonella spp., Salmonella enterica serovar Paratyphi, Salmonella enterica serovar Typhi, Shigella spp., Streptococcus suis, and Vibrio spp. infections. We tested the tool in six hospitals in Thailand in 2022. The total number of deaths identified by the AMASSplus was higher than those reported to the national notifiable disease surveillance system (NNDSS); particularly for B. pseudomallei infection (134 versus 2 deaths). This tool could support the NNDSS in LMICs.

Identifying villages and breeding habitats for dengue transmission in Thailand: insights from long-term larval surveys.

BACKGROUND: In Thailand, the Department of Disease Control (DDC) regularly performs visual larval surveys throughout the country to monitor dengue fever outbreaks. Since 2016, the DDC switched from a paper-based to a digital-based larval survey process. The significant amount of larval survey data collected digitally presents a valuable opportunity to precisely identify the villages and breeding habitats that are vulnerable to dengue transmission. METHODS: The study used digitally collected larval survey data from 2017 to 2019. It employed larval indices to evaluate the risk of dengue transmission in villages based on seasonal, regional, and categorical perspectives. Furthermore, the study comprehensively scrutinized each container category by employing different measures to determine its breeding preference ratio. RESULTS: The result showed that villages with a very high-risk of dengue transmission were present year-round in all regions, with the highest proportion during the rainy season. The Southern region had more high-risk villages during the winter season due to rainfall. Slums and residential communities were more vulnerable to dengue than commercial areas. All container categories could potentially serve as breeding habitats for dengue-carrying mosquitoes, with abandoned containers being the most significant breeding sites. CONCLUSIONS: The risk of dengue transmission was present year-round throughout Thailand. This underscores the importance of community and government initiatives, along with sustained public awareness campaigns and active community engagement, to efficiently and permanently eradicate mosquito breeding habitats. It should be noted that larval indices may not strongly correlate with dengue cases, as indicated by the preliminary analysis. However, they offer valuable insights into potential breeding sites for targeted preventive measures.

Characteristics, risk factors, and outcomes related to Zika virus infection during pregnancy in Northeastern Thailand: A prospective pregnancy cohort study, 2018-2020.

BACKGROUND: In response to the 2015-2016 Zika virus (ZIKV) outbreak and the causal relationship established between maternal ZIKV infection and adverse infant outcomes, we conducted a cohort study to estimate the incidence of ZIKV infection in pregnancy and assess its impacts in women and infants. METHODOLOGY/PRINCIPAL FINDINGS: From May 2018-January 2020, we prospectively followed pregnant women recruited from 134 participating hospitals in two non-adjacent provinces in northeastern Thailand. We collected demographic, clinical, and epidemiologic data and blood and urine at routine antenatal care visits until delivery. ZIKV infections were confirmed by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Specimens with confirmed ZIKV underwent whole genome sequencing. Among 3,312 women enrolled, 12 (0.36%) had ZIKV infections, of which two (17%) were detected at enrollment. Ten (83%, 3 in 2nd and 7 in 3rd trimester) ZIKV infections were detected during study follow-up, resulting in an infection rate of 0.15 per 1,000 person-weeks (95% CI: 0.07-0.28). The majority (11/12, 91.7%) of infections occurred in one province. Persistent ZIKV viremia (42 days) was found in only one woman. Six women with confirmed ZIKV infections were asymptomatic until delivery. Sequencing of 8 ZIKV isolates revealed all were of Asian lineage. All 12 ZIKV infected women gave birth to live, full-term infants; the only observed adverse birth outcome was low birth weight in one (8%) infant. Pregnancies in 3,300 ZIKV-rRT-PCR-negative women were complicated by 101 (3%) fetal deaths, of which 67 (66%) had miscarriages and 34 (34%) had stillbirths. There were no differences between adverse fetal or birth outcomes of live infants born to ZIKV-rRT-PCR-positive mothers compared to live infants born to ZIKV-rRT-PCR-negative mothers. CONCLUSIONS/SIGNIFICANCE: Confirmed ZIKV infections occurred infrequently in this large pregnancy cohort and observed adverse maternal and birth outcomes did not differ between mothers with and without confirmed infections.

Collective activities of the Thai Coordinating Unit for One Health (CUOH): Past activities and future directions.

In Thailand, One Health concepts have been implemented among government agencies, academic institutions, intergovernment, and civil society organizations. The Thai Coordinating Unit for One Health (CUOH) was established as a collaborating body for One Health-related activities in the country in 2014. To better understand what activities CUOH has completed thus far and to assess future activities, we conducted a network analysis to identify and visualize linkages between organizations and activities from 2015 to 2021. Activities were divided into four categories: organizing meetings, developing products, providing funds, and managing resources. Most of the 114 CUOH-managed meeting participants were representatives from 72 government and 20 academic institutions. The Thai Ministry of Public Health's Department of Disease Control participated in 148 meetings, the highest attendance among all organizations working with CUOH. The first CUOH guideline or manual was published in 2020, and 11 were published in 2021. In funding management, the CUOH worked with 25 organizations to carry out 71 projects from 2015 to 2021. Additionally, the CUOH played an important role in allocating COVID-19 vaccines during the COVID-19 pandemic. The CUOH has connected organizations working in different health sectors to collaborate jointly through meetings and projects that use a One Health approach, which can holistically improve health management in Thailand. Diverse funding sources are needed to ensure the sustainability of the unit in the future.

Protective Role of NS1-Specific Antibodies in the Immune Response to Dengue Virus through Antibody-Dependent Cellular Cytotoxicity.

BACKGROUND: Dengue virus (DENV) non-structural protein 1 (NS1) has multiple functions within infected cells, on the cell surface, and in secreted form, and is highly immunogenic. Immunity from previous DENV infections is known to exert both positive and negative effects on subsequent DENV infections, but the contribution of NS1-specific antibodies to these effects is incompletely understood. METHODS: We investigated the functions of NS1-specific antibodies and their significance in DENV infection. We analyzed plasma samples collected in a prospective cohort study prior to symptomatic or subclinical secondary DENV infection. We measured binding to purified recombinant NS1 protein and to NS1-expressing CEM cells, antibody-mediated NK cell activation by plate-bound NS1 protein, and antibody-dependent cellular cytotoxicity (ADCC) of NS1-expressing target cells. RESULTS: We found that antibody responses to NS1 were highly serotype-cross-reactive and that subjects who experienced subclinical DENV infection had significantly higher antibody responses to NS1 in pre-infection plasma than subjects who experienced symptomatic infection. We observed strong positive correlations between antibody binding and NK activation. CONCLUSIONS: These findings demonstrate the involvement of NS1-specific antibodies in ADCC and provide evidence for a protective effect of NS1-specific antibodies in secondary DENV infection.

Integration of population-level data sources into an individual-level clinical prediction model for dengue virus test positivity.

The differentiation of dengue virus (DENV) infection, a major cause of acute febrile illness in tropical regions, from other etiologies, may help prioritize laboratory testing and limit the inappropriate use of antibiotics. While traditional clinical prediction models focus on individual patient-level parameters, we hypothesize that for infectious diseases, population-level data sources may improve predictive ability. To create a clinical prediction model that integrates patient-extrinsic data for identifying DENV among febrile patients presenting to a hospital in Thailand, we fit random forest classifiers combining clinical data with climate and population-level epidemiologic data. In cross-validation, compared to a parsimonious model with the top clinical predictors, a model with the addition of climate data, reconstructed susceptibility estimates, force of infection estimates, and a recent case clustering metric significantly improved model performance.

Household immunity and individual risk of infection with dengue virus in a prospective, longitudinal cohort study.

Although it is known that household infections drive the transmission of dengue virus (DENV), it is unclear how household composition and the immune status of inhabitants affect the individual risk of infection. Most population-based studies to date have focused on paediatric cohorts because more severe forms of dengue mainly occur in children, and the role of adults in dengue transmission is understudied. Here we analysed data from a multigenerational cohort study of 470 households, comprising 2,860 individuals, in Kamphaeng Phet, Thailand, to evaluate risk factors for DENV infection. Using a gradient-boosted regression model trained on annual haemagglutination inhibition antibody titre inputs, we identified 1,049 infections, 90% of which were subclinical. By analysing imputed infections, we found that individual antibody titres, household composition and antibody titres of other members in the same household affect an individual's risk of DENV infection. Those individuals living in households with high average antibody titres, or households with more adults, had a reduced risk of infection. We propose that herd immunity to dengue acts at the household level and may provide insight into the drivers of the recent change in the shifting age distribution of dengue cases in Thailand.

Children orphaned from COVID-19 in Thailand: maximize use of civil registration database for policies.

Orphans, especially those who experience maternal loss at a young age, face significant long-term negative impacts on their lives and psychological well-being, extending beyond the age of 18. As of July 2023, the global death toll of COVID-19 has reached 6.9 million, leaving behind an unknown number of orphans who require immediate attention and support from policymakers. In Thailand, from April 2020 to July 2022, the total number of COVID-19-related deaths reached 42,194, resulting in 4,139 parental orphans. Among them, 452 (10.9%) were children under the age of five, who are particularly vulnerable and necessitate special policy attention and ongoing support. While the provision of 12 years of free education for all and Universal Health Coverage helps alleviate the education and health expenses borne by households supporting these orphans, the monthly government support of 2,000 Baht until the age of 18 is insufficient to cover their living costs and other education-related expenditures. We advocate for adequate financial and social support for COVID-19 orphans, emphasizing the importance of placing them with relatives rather than institutional homes. In the context of post-pandemic recovery, this perspective calls upon governments and global communities to estimate the number of orphans and implement policies to safeguard and support them in the aftermath of COVID-19.

Maternally derived antibody titer dynamics and risk of hospitalized infant dengue disease.

Infants less than 1 y of age experience high rates of dengue disease in dengue virus (DENV) endemic countries. This burden is commonly attributed to antibody-dependent enhancement (ADE), whereby concentrations of maternally derived DENV antibodies become subneutralizing, and infection-enhancing. Understanding antibody-related mechanisms of enhanced infant dengue disease risk represents a significant challenge due to the dynamic nature of antibodies and their imperfect measurement processes. Further, key uncertainties exist regarding the impact of long-term shifts in birth rates, population-level infection risks, and maternal ages on the DENV immune landscape of newborns and their subsequent risks of severe dengue disease in infancy. Here, we analyze DENV antibody data from two infant cohorts (N = 142 infants with 605 blood draws) and 40 y of infant dengue hospitalization data from Thailand. We use mathematical models to reconstruct maternally derived antibody dynamics, accounting for discretized measurement processes and limits of assay detection. We then explore possible antibody-related mechanisms of enhanced infant dengue disease risk and their ability to reconstruct the observed age distribution of hospitalized infant dengue cases. We find that ADE mechanisms are best able to reconstruct the observed data. Finally, we describe how the shifting epidemiology of dengue in Thailand, combined with declining birth rates, have decreased the absolute risk of infant dengue disease by 88% over a 40-y period while having minimal impact on the mean age of infant hospitalized dengue disease.

Integration of population-level data sources into an individual-level clinical prediction model for dengue virus test positivity.

The differentiation of dengue virus (DENV) infection, a major cause of acute febrile illness in tropical regions, from other etiologies, may help prioritize laboratory testing and limit the inappropriate use of antibiotics. While traditional clinical prediction models focus on individual patient-level parameters, we hypothesize that for infectious diseases, population-level data sources may improve predictive ability. To create a clinical prediction model that integrates patient-extrinsic data for identifying DENV among febrile patients presenting to a hospital in Thailand, we fit random forest classifiers combining clinical data with climate and population-level epidemiologic data. In cross validation, compared to a parsimonious model with the top clinical predictors, a model with the addition of climate data, reconstructed susceptibility estimates, force of infection estimates, and a recent case clustering metric, significantly improved model performance.

Impact of COVID-19 Vaccination Rates and Public Measures on Case Rates at the Provincial Level, Thailand, 2021: Spatial Panel Model Analyses.

The coronavirus disease of 2019 (COVID-19) was a pandemic that caused high morbidity and mortality worldwide. The COVID-19 vaccine was expected to be a game-changer for the pandemic. This study aimed to describe the characteristics of COVID-19 cases and vaccination in Thailand during 2021. An association between vaccination and case rates was estimated with potential confounders at ecological levels (color zones, curfews set by provincial authorities, tourism, and migrant movements) considering time lags at two, four, six, and eight weeks after vaccination. A spatial panel model for bivariate data was used to explore the relationship between case rates and each variable and included only a two-week lag after vaccination for each variable in the multivariate analyses. In 2021, Thailand had 1,965,023 cumulative cases and 45,788,315 total administered first vaccination doses (63.60%). High cases and vaccination rates were found among 31-45-year-olds. Vaccination rates had a slightly positive association with case rates due to the allocation of hot-spot pandemic areas in the early period. The proportion of migrants and color zones measured had positive associations with case rates at the provincial level. The proportion of tourists had a negative association. Vaccinations should be provided to migrants, and collaboration between tourism and public health should prepare for the new era of tourism.

SARS-CoV-2 Variants Detection Strategies in Wastewater Samples Collected in the Bangkok Metropolitan Region.

Wastewater surveillance is considered a promising approach for COVID-19 surveillance in communities. In this study, we collected wastewater samples between November 2020 and February 2022 from twenty-three sites in the Bangkok Metropolitan Region to detect the presence of SARS-CoV-2 and its variants for comparison to standard clinical sampling. A total of 215 wastewater samples were collected and tested for SARS-CoV-2 RNA by real-time PCR with three targeted genes (N, E, and ORF1ab); 102 samples were positive (42.5%). The SARS-CoV-2 variants were determined by a multiplex PCR MassARRAY assay to distinguish four SARS-CoV-2 variants, including Alpha, Beta, Delta, and Omicron. Multiple variants of Alpha-Delta and Delta-Omicron were detected in the wastewater samples in July 2021 and January 2022, respectively. These wastewater variant results mirrored the country data from clinical specimens deposited in GISAID. Our results demonstrated that wastewater surveillance using multiple signature mutation sites for SARS-CoV-2 variant detection is an appropriate strategy to monitor the presence of SARS-CoV-2 variants in the community at a low cost and with rapid turn-around time. However, it is essential to note that sequencing surveillance of wastewater samples should be considered complementary to whole genome sequencing of clinical samples to detect novel variants.

Economic Evaluation of Evusheld for Preexposure Prevention of COVID-19 in High-Risk Populations: Early Evidence from Thailand.

BACKGROUND AND AIMS: The introduction of Coronavirus disease 2019 (COVID-19) vaccines urged all Thais to seek prevention of serious illness and death from COVID-19. However, immunocompromised individuals might not be able to achieve an efficient immune response from these vaccines. This study aimed to evaluate the cost-effectiveness and budget impact of introducing Evusheld (tixagevimab plus cilgavimab) for three patient groups-organ transplant, autoimmune disease, and dialysis patients, from the Thai government perspective. METHODS: A Markov decision model was developed to compare the use of Evusheld plus COVID-19 vaccines versus COVID-19 vaccines alone. The methodology followed the National HTA Guidelines of Thailand. Model input parameters were collected locally from retrospective data and from a literature review. RESULTS: Evusheld helped prevent COVID-19 infection, severe infection, and death in all three patient groups. Using the Thai threshold of 160,000 Thai Baht (THB) per quality-adjusted life year (QALY) gained, the only scenario found to be cost-effective was that of dialysis patients with inadequate immune response, with an incremental cost-effectiveness ratio (ICER) of 54,700 THB per QALY gained. To make a policy of Evusheld provision cost-effective in other groups, the price of Evusheld had to be lower (a reduction of 44-88% of its current price). The results of one-way sensitivity analysis indicated that the cost-effectiveness of Evusheld was sensitive to changes in the rate of infection, cost and efficacy of Evusheld, proportion of inadequate immune responses, and the probability of moving from a 'recovered' to 'susceptible' status. CONCLUSION: Among three COVID-19-vaccinated immunocompromised patient populations, this study concluded that Evusheld was cost-effective for dialysis patients with inadequate immune response to the COVID-19 vaccine.

Effectiveness of heterologous third and fourth dose COVID-19 vaccine schedules for SARS-CoV-2 infection during delta and omicron predominance in Thailand: a test-negative, case-control study.

Background: The Coronavirus disease 2019 (COVID-19) pandemic has evolved quickly, with numerous waves of different variants of concern resulting in the need for countries to offer continued protection through booster vaccination. To ensure adequate vaccination coverage, Thailand has proactively adopted heterologous vaccination schedules. While randomised controlled trials have assessed homologous schedules in detail, limited data has been reported for heterologous vaccine effectiveness (VE). Methods: Utilising a unique active surveillance network established in Chiang Mai, Northern Thailand, we conducted a test-negative case control study to assess the VE of heterologous third and fourth dose schedules against SARS-CoV-2 infection among suspect-cases during Oct 1-Dec 31, 2021 (delta-predominant) and Feb 1-Apr 10, 2022 (omicron-predominant) periods. Findings: After a third dose, effectiveness against delta infection was high (adjusted VE 97%, 95% CI 94-99%) in comparison to moderate protection against omicron (adjusted VE 31%, 95% CI 26-36%). Good protection was observed after a fourth dose (adjusted VE 75%, 95% CI 71-80%). VE was consistent across age groups for both delta and omicron infection. The VE of third or fourth doses against omicron infection were equivalent for the three main vaccines used for boosting in Thailand, suggesting coverage, rather than vaccine type is a much stronger predictor of protection. Interpretation: Appropriately timed booster doses have a high probability of preventing COVID-19 infection with both delta and omicron variants. Our evidence supports the need for ongoing national efforts to increase population coverage of booster doses. Funding: This research was supported by the National Research Council of Thailand (NRCT) under The Smart Emergency Care Services Integration (SECSI) project to Faculty of Public Health Chiang Mai University.

Correction: Challenges in Real-Time Prediction of Infectious Disease: A Case Study of Dengue in Thailand.

[This corrects the article DOI: 10.1371/journal.pntd.0004761.].

Evidence of transmission of influenza A and influenza B co-infection in healthcare workers.

INTRODUCTION: Co-infection of influenza A and B has been reported, especially in outbreak situations, but epidemiological and clinical information is limited. We aimed to investigate an outbreak of influenza among health care workers in which the index case suffered from influenza A and B co-infection. METHODOLOGY: We investigated the outbreak setting through the utilization of structural questionnaires, molecular methods, and serological tests. RESULTS: Among 13 persons, one index case and five confirmed secondary cases were confirmed. The overall influenza infection rate was 46.2% (6/13), with infection rates for influenza A and B at 38.5% (5/13) and 23.1% (3/13), respectively. Interestingly, one of the secondary cases had influenza A and B co-infection identical to the index case. There was no significant association between vaccination status and influenza infection. CONCLUSIONS: This study unveils the demonstration of human-to-human influenza A and B co-infection transmission for the first time. Surveillance systems, combined with epidemiological case investigation comprising molecular diagnosis, should be strengthened for future influenza outbreak preparedness.

Assessing the role of multiple mechanisms increasing the age of dengue cases in Thailand.

The mean age of dengue hemorrhagic fever (DHF) cases increased considerably in Thailand from 8.1 to 24.3 y between 1981 and 2017 (mean annual increase of 0.45 y). Alternative proposed explanations for this trend, such as changes in surveillance practices, reduced mosquito­human contact, and shifts in population demographics, have different implications for global dengue epidemiology. To evaluate the contribution of each of these hypothesized mechanisms to the observed data, we developed 20 nested epidemiological models of dengue virus infection, allowing for variation over time in population demographics, infection hazards, and reporting rates. We also quantified the effect of removing or retaining each source of variation in simulations of the age trajectory. Shifts in the age structure of susceptibility explained 58% of the observed change in age. Adding heterogeneous reporting by age and reductions in per-serotype infection hazard to models with shifts in susceptibility explained an additional 42%. Reductions in infection hazards were mostly driven by changes in the number of infectious individuals at any time (another consequence of shifting age demographics) rather than changes in the transmissibility of individual infections. We conclude that the demographic transition drives the overwhelming majority of the observed change as it changes both the age structure of susceptibility and the number of infectious individuals. With the projected Thai population age structure, our results suggest a continuing increase in age of DHF cases, shifting the burden toward individuals with more comorbidity. These insights into dengue epidemiology may be relevant to many regions of the globe currently undergoing comparable changes in population demographics.

Individual, Household, and Community Drivers of Dengue Virus Infection Risk in Kamphaeng Phet Province, Thailand.

BACKGROUND: Dengue virus (DENV) often circulates endemically. In such settings with high levels of transmission, it remains unclear whether there are risk factors that alter individual infection risk. METHODS: We tested blood taken from individuals living in multigenerational households in Kamphaeng Phet province, Thailand for DENV antibodies (N = 2364, mean age 31 years). Seropositivity ranged from 45.4% among those 1-5 years old to 99.5% for those >30 years. Using spatially explicit catalytic models, we estimated that 11.8% of the susceptible population gets infected annually. RESULTS: We found that 37.5% of the variance in seropositivity was explained by unmeasured household-level effects with only 4.2% explained by spatial differences between households. The serostatus of individuals from the same household remained significantly correlated even when separated by up to 15 years in age. CONCLUSIONS: These findings show that despite highly endemic transmission, persistent differences in infection risk exist across households, the reasons for which remain unclear.