Heterologous Ad26.COV2.S booster after primary BBIBP-CorV vaccination against SARS-CoV-2 infection: 1-year follow-up of a phase 1/2 open-label trial.

BACKGROUND: Inactivated whole-virus vaccination elicits immune responses to both SARS-CoV-2 nucleocapsid (N) and spike (S) proteins, like natural infections. A heterologous Ad26.COV2.S booster given at two different intervals after primary BBIBP-CorV vaccination was safe and immunogenic at days 28 and 84, with higher immune responses observed after the longer pre-boost interval. We describe booster-specific and hybrid immune responses over 1 year. METHODS: This open-label phase 1/2 study was conducted in healthy Thai adults aged ≥ 18 years who had completed primary BBIBP-CorV primary vaccination between 90-240 (Arm A1; n = 361) or 45-75 days (Arm A2; n = 104) before enrolment. All received an Ad26.COV2.S booster. We measured anti-S and anti-N IgG antibodies by Elecsys®, neutralizing antibodies by SARS-CoV-2 pseudovirus neutralization assay, and T-cell responses by quantitative interferon (IFN)-γ release assay. Immune responses were evaluated in the baseline-seronegative population (pre-booster anti-N < 1.4 U/mL; n = 241) that included the booster-effect subgroup (anti-N < 1.4 U/mL at each visit) and the hybrid-immunity subgroup (anti-N ≥ 1.4 U/mL and/or SARS-CoV-2 infection, irrespective of receiving non-study COVID-19 boosters). RESULTS: In Arm A1 of the booster-effect subgroup, anti-S GMCs were 131-fold higher than baseline at day 336; neutralizing responses against ancestral SARS-CoV-2 were 5-fold higher than baseline at day 168; 4-fold against Omicron BA.2 at day 84. IFN-γ remained approximately 4-fold higher than baseline at days 168 and 336 in 18-59-year-olds. Booster-specific responses trended lower in Arm A2. In the hybrid-immunity subgroup at day 336, anti-S GMCs in A1 were 517-fold higher than baseline; neutralizing responses against ancestral SARS-CoV-2 and Omicron BA.2 were 28- and 31-fold higher, respectively, and IFN-γ was approximately 14-fold higher in 18-59-year-olds at day 336. Durable immune responses trended lower in ≥ 60-year-olds. CONCLUSION: A heterologous Ad26.COV2.S booster after primary BBIBP-CorV vaccination induced booster-specific immune responses detectable up to 1 year that were higher in participants with hybrid immunity. CLINICAL TRIALS REGISTRATION: NCT05109559.

Health Utility Score in Thai Patients with Chronic Rhinosinusitis: Pre- and Postoperative Analyses.

BACKGROUND: Endoscopic sinus surgery (ESS) can increase the health utility score (HUS) of patients with chronic rhinosinusitis (CRS) who require the surgery. HUS varies depending on the geographical or living environment. HUS in CRS has never been evaluated in Thailand. The objective of this study was to evaluate the HUS of Thai patients with CRS before and after ESS through multiple approaches. METHODS: Thai patients (age ≥ 18) with CRS scheduled for ESS were enrolled in this prospective study. The preoperative (baseline) demographics, 22-items sinonasal outcome test, endoscopic score, and CT score were recorded. The HUS was evaluated using four methods: the EuroQoL-5 Dimension-5 level (EQ-5D-5L), Visual Analog Scale (VAS), Standard gamble (SG), and Time trade-off (TTO); at baseline, three months and six months post-operation. RESULTS: Data from 60 patients were analyzed. The mean baseline HUS scores by EQ-5D-5L, VAS, SG, and TTO were 0.75, 0.65, 0.79, and 0.85, respectively. The postoperative HUS significantly improved to 0.96, 0.91, 0.96, 0.97 at three months, and 0.97, 0.92, 0.97, and 0.98 at six months, respectively. ESS raised the HUS by 0.12-0.27 points. Among the four methods, VAS showed the lowest HUS at all time points. CONCLUSION: The preoperative HUS in Thai patients with CRS generally increased to near-perfect values after the ESS. The increase in HUS reflecting the improved general quality of life, was demonstrated at three and up to six months after ESS. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2070-2076, 2024.

Assessment of malaria risk in Southeast Asia: a systematic review.

BACKGROUND: Several countries in Southeast Asia are nearing malaria elimination, yet eradication remains elusive. This is largely due to the challenge of focusing elimination efforts, an area where risk prediction can play an essential supporting role. Despite its importance, there is no standard numerical method to quantify the risk of malaria infection. Thus, there is a need for a consolidated view of existing definitions of risk and factors considered in assessing risk to analyse the merits of risk prediction models. This systematic review examines studies of the risk of malaria in Southeast Asia with regard to their suitability in addressing the challenges of malaria elimination in low transmission areas. METHODS: A search of four electronic databases over 2010-2020 retrieved 1297 articles, of which 25 met the inclusion and exclusion criteria. In each study, examined factors included the definition of the risk and indicators of malaria transmission used, the environmental and climatic factors associated with the risk, the statistical models used, the spatial and temporal granularity, and how the relationship between environment, climate, and risk is quantified. RESULTS: This review found variation in the definition of risk used, as well as the environmental and climatic factors in the reviewed articles. GLM was widely adopted as the analysis technique relating environmental and climatic factors to malaria risk. Most of the studies were carried out in either a cross-sectional design or case-control studies, and most utilized the odds ratio to report the relationship between exposure to risk and malaria prevalence. CONCLUSIONS: Adopting a standardized definition of malaria risk would help in comparing and sharing results, as would a clear description of the definition and method of collection of the environmental and climatic variables used. Further issues that need to be more fully addressed include detection of asymptomatic cases and considerations of human mobility. Many of the findings of this study are applicable to other low-transmission settings and could serve as a guideline for further studies of malaria in other regions.

Gametocyte prevalence and risk factors of P. falciparum malaria patients admitted at the Hospital for Tropical Diseases, Thailand: a 20-year retrospective study.

BACKGROUND: The incidence of malaria in Thailand has dramatically declined over the past two decades, and the goal is to eliminate malaria by 2025. Despite significant progress, one of the key challenges to malaria elimination are undetected gametocyte carriers. Human migration adds complexity to the malaria situation, as it not only sustains local transmission but also poses the risk of spreading drug-resistant parasites. Currently, no study has assessed the prevalence of gametocytes across multiple years in Plasmodium falciparum malaria patients in Thailand, and the risk factors for gametocyte carriage have not been fully explored. METHODS: Medical records of all P. falciparum malaria patients admitted from January 1, 2001 to December 31, 2020 at the Hospital for Tropical Diseases, Thailand, were retrospectively examined and a total of 1962 records were included for analysis. Both P. falciparum parasites and gametocytes were diagnosed by microscopy. A regression model was used to evaluate predictors of gametocyte carriage. RESULTS: The study demonstrated gametocyte prevalence in low malaria transmission areas. Nine risk factors for gametocyte carriage were identified: age between 15 and 24 years [adjusted odds ratio (aOR) = 1.96, 95% confidence interval (CI) 1.18-3.26], Karen ethnicity (aOR = 2.59, 95% CI 1.56-4.29), preadmission duration of fever > 7 days (aOR = 5.40, 95% CI 3.92-7.41), fever on admission (> 37.5 °C) (aOR = 0.61, 95% CI 0.48-0.77), haemoglobin ≤ 8 g/dL (aOR = 3.32, 95% CI 2.06-5.33), asexual parasite density > 5000-25,000/µL (aOR = 0.71, 95% CI 0.52-0.98), asexual parasite density > 25,000-100,000/µL (aOR = 0.74, 95% CI 0.53-1.03), asexual parasite density > 100,000/µL (aOR = 0.51, 95% CI 0.36-0.72), platelet count ≤ 100,000/µL (aOR = 0.65, 95% CI 0.50-0.85, clinical features of severe malaria (aOR = 2.33, 95% CI 1.76-3.10) and dry season (aOR = 1.41, 95% CI 1.10-1.80). An increasing incidence of imported transnational malaria cases was observed over the past two decades. CONCLUSIONS: This is the first study to determine the prevalence of gametocytes among patients with symptomatic P. falciparum malaria, identify the risk factors for gametocyte carriage, and potential gametocyte carriers in Thailand. Blocking transmission is one of the key strategies for eliminating malaria in these areas. The results might provide important information for targeting gametocyte carriers and improving the allocation of resources for malaria control in Thailand. This study supports the already nationally recommended use of a single dose of primaquine in symptomatic P. falciparum malaria patients to clear gametocytes.

Interventions for promoting patients' adherence to 14-day primaquine treatment in a highly malaria-endemic township in Myanmar: a qualitative study among key stakeholders.

BACKGROUND: Plasmodium vivax malaria is considered a major threat to malaria eradication. The radical cure for P. vivax malaria normally requires a 14-day administration of primaquine (PQ) to clear hypnozoites. However, maintaining adherence to PQ treatment is a significant challenge, particularly in malaria-endemic rural areas. Hence, this study aimed to formulate interventions for promoting patients' commitment to PQ treatment in a highly malaria-endemic township in Myanmar. METHODS: A qualitative study was conducted in Waingmaw Township in northern Myanmar, where P. vivax malaria is highly endemic. Key stakeholders including public health officers and community members participated in focus group discussions (FGDs) and in-depth interviews (IDIs) in September 2022. Data were collected using validated guidelines, translated into English, and visualized through thematic analysis. RESULTS: Responsible individuals from different levels of the Myanmar National Malaria Control Programme participated in the IDIs. Most of them reported being aware of the markedly increasing trend of P. vivax and the possibility of relapse cases, especially among migrants who are lost to follow-up. Workload was a key concern surrounding intervention implementation. The respondents discussed possible interventions, such as implementing directly observed treatment (DOT) by family members, piloting a shorter PQ regimen, expanding the community's malaria volunteer network, and strengthening health education activities using local languages to promote reasonable drug adherence. FGDs among community members revealed that although people were knowledgeable about malaria symptoms, places to seek treatment, and the use of bed nets to prevent mosquito bites, most of them still preferred to be treated by quack doctors and rarely used insecticide-treated nets at worksites. Many often stopped taking the prescribed drugs once the symptoms disappeared. Nevertheless, some respondents requested more bed nets to be distributed and health promotion activities to be conducted. CONCLUSION: In rural areas where human resources are limited, interventions such as implementing family member DOT or shortening PQ regimens should be introduced to enhance the radical cure for the P. vivax infection. Disseminating information about the importance of taking the entire treatment course and emphasizing the burden of relapse is also essential.

Interventions for promoting patients' adherence to 14-day primaquine treatment in a highly malaria-endemic township in Myanmar: A qualitative study among key stakeholders.

Background: Plasmodium vivax malaria is considered a major threat to malaria eradication. The radical cure for P. vivax malaria normally requires a 14-day administration of primaquine (PQ) to clear hypnozoites. However, maintaining adherence to PQ treatment is a significant challenge, particularly in malaria-endemic rural areas. Hence, this study aimed to formulate interventions for promoting patients' commitment to PQ treatment in a highly malaria-endemic township in Myanmar. Methods: A qualitative study was conducted in Waingmaw Township in northern Myanmar, where P. vivax malaria is highly endemic. Key stakeholders including public health officers and community members participated in focus group discussions (FGDs) and in-depth interviews (IDIs) in September 2022. Data were collected using validated guidelines, translated into English, and visualized through thematic analysis. Results: Responsible individuals from different levels of the Myanmar National Malaria Control Program participated in the IDIs. Most of them reported being aware of the markedly increasing trend of P. vivax and the possibility of relapse cases, especially among migrants who are lost to follow-up. Workload was a key concern surrounding intervention implementation. The respondents discussed possible interventions, such as implementing directly observed treatment (DOT) by family members, piloting a shorter PQ regimen, expanding the community's malaria volunteer network, and strengthening health education activities using local languages to promote reasonable drug adherence. FGDs among community members revealed that although people were knowledgeable about malaria symptoms, places to seek treatment, and the use of bed nets to prevent mosquito bites, most of them still preferred to be treated by quack doctors and rarely used insecticide-treated nets at worksites. Many often stopped taking the prescribed drugs once the symptoms disappeared. Nevertheless, some respondents requested more bed nets to be distributed and health promotion activities to be conducted. Conclusion: In rural areas where human resources are limited, interventions such as implementing family member DOT or shortening PQ regimens should be introduced to enhance the radical cure for the P. vivax infection. Disseminating information about the importance of taking the entire treatment course and emphasizing the burden of relapse is also essential.

Prevalence of hypertension among travelers and stability of blood pressure control during travel: a cross-sectional descriptive study and prospective cohort study.

BACKGROUND: Hypertension is a common and important risk factor for cardiovascular disease which is the leading cause of death among the general population and travelers. Data on hypertension among travelers are very limited due to the scarcity of research reports in this specific population. Therefore, this study aimed to determine the prevalence of hypertension among adult travelers and the stability of blood pressure control during international trips using a mobile automated blood pressure device. METHODS: This was a cross-sectional descriptive study conducted at the Thai travel clinic, Hospital for Tropical Diseases in Bangkok, Thailand. All adult travelers completed a questionnaire which included demographic data, medical history, medication use, trip characteristics and hypertension awareness and knowledge. Standard two time blood pressure measurements were performed at the clinic to detect possible undiagnosed hypertension. Travelers with pre-existing hypertension were also invited to monitor their blood pressure level before and during their trip for a total of 14 days by using an automated blood pressure device and reporting the readings back to the study team. RESULT: During July and October 2022, a total of 1,359 adult travelers visited the Thai Travel Clinic before their international trip. The overall prevalence of hypertension was 28.8%, including those with pre-existing hypertension (6.7%) and those with newly diagnosed hypertension (22.2%). Travelers with newly diagnosed hypertension were significantly younger than travelers with pre-existing hypertension (38.5 years vs. 55.6 years, p < 0.001). Eleven travelers agreed to monitor their blood pressure, Most (90.9%, 10/11) had stable blood pressure control during their trip. One participant had > 10 mmHg higher blood pressure during the trip, however this was not clinically significant. All participants remained well, and acute symptoms secondary to hypertension were not reported. CONCLUSION: Up to 28.8% of adult travelers seen in pre-travel consultations had hypertension. Most of them were unaware of their blood pressure condition. Vital signs including blood pressure should be evaluated in all pre-travel visits in order to prevent undiagnosed severe hypertension that might lead to hypertensive crisis.

A cost-effectiveness analysis of the 13-valent pneumococcal conjugated vaccine and the 23-valent pneumococcal polysaccharide vaccine among Thai older adult.

Introduction: This study aims to assess the economic impact of introducing the 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) to Thai older adult aged ≥ 65 years who are healthy or with chronic health conditions and immunocompromised conditions from a societal perspective in order to introduce the vaccine to Thailand's National Immunization Program for the older adult. Methods: A Markov model was adopted to simulate the natural history and economic outcomes of invasive pneumococcal diseases using updated published sources and Thai databases. We reported analyses as incremental cost-effectiveness ratios (ICER) in USD per quality-adjusted life year (QALY) gained. In addition, sensitivity analyses and budget impact analyses were conducted. Results: The base-case analysis of all interventions (no vaccinations [current standard of care in Thailand], PPSV23, and PCV13) showed that PPSV23 was extendedly dominated by PCV13. Among healthy individuals or those with chronic health conditions, ICER for PCV13 was 233.63 USD/QALY; meanwhile, among individuals with immunocompromised conditions, ICER for PCV13 was 627.24 USD/QALY. PCV13 are economical vaccine for all older adult Thai individuals when compared to all interventions. Conclusions: In the context of Thailand, PCV13 is recommended as the best buy and should be primarily prioritized when both costs and benefits are considered. Also, this model will be beneficial to the two-next generation pneumococcal vaccines implementation in Thailand.

Efficacy of household Aedes larval control practices in a peri-urban township, Yangon, Myanmar: Implication for entomological surveillance.

Dengue is a major public health concern in Myanmar. We carried out a cross-sectional study to investigate the efficacy of larval control practices in household water containers, such as the use of the larvicide, temephos, covering the containers with lids and weekly cleaning. We surveyed 300 households in Kaw Hmu Township, a peri-urban community in the Yangon region. We inspected 1,892 water storage containers and 342 non-water storage/household waste containers during the rainy season and 1,866 water storage containers and 287 non-water storage/household waste containers during the dry season. The presence of Aedes larvae and larval control measures were recorded for each container. Results revealed that larval indices were higher than World Health Organization standard indices, and infestations in water storage containers were more common in the rainy season (6.6%) than in the dry season (5.7%). Infestations were also more likely in containers of non-potable water (9.1%-9.9%) than in containers of potable water (0.1%-0.7%). Two thirds of water storage containers were treated with temephos. Containers most likely to contain Aedes larvae were cement basins and barrels. Temephos was effective in controlling infestations in cement basins, while weekly cleaning was effective in controlling infestations in barrels. Combinations of control methods were more effective at larval control than the use of a single method. Larval infestations were high (18.4% in the rainy season) in unused containers and in containers which were household waste. Overall, we found a complex interaction between household water use, container characteristics, and larval control practices. Larval control strategies in Myanmar will require ongoing entomological surveillance and the identification of key breeding sources and optimal control methods.

Effectiveness of dengue training programmes on prevention and control among high school students in the Yangon region, Myanmar.

Background: Dengue is one of the health problems in Myanmar. Thus, health promotion in schools is considered a key approach for reducing risk-taking behaviours related to dengue. Objectives: The study aimed to evaluate a dengue training programme for high school students to measure changes in knowledge, attitude and practices (KAP) towards dengue; evaluate the effectiveness of the programme in improving prevention and control practices among families and determining changes in larval indices in their dwelling places. Methodology: The dengue school training programme was conducted for Grades 9 and 10 students in Yangon. In total, 300 students in the intervention school received training and were compared with 300 students as control. KAP was assessed using a self-administered questionnaire, whereas larval and control practice surveys were conducted at the homes of both groups 3 months before and after the programme. Results: The KAP scores of the intervention group increased after the programme. Moreover, the programme improved prevention and control practices and decreased the larval indices in the intervention group. Students from the same group with high scores in knowledge and self-reported practices were less likely to exhibit Aedes larval positivity in their residential areas. Conclusion: This study demonstrated the impact of the dengue training programme on the KAP of students and short-term family larval control practices, which influenced household larval indices.

International University Students' Pre-Travel Preparation, Knowledge and Practices towards Travel Health in Thailand: A Nationwide Cross-Sectional Study.

International university students are vulnerable travellers due to their unpredictable schedules and lifestyles. As Thailand continues to see an increase in international students, evaluating their pre-travel preparation and preventive behaviours is crucial to identify areas for improvement. For this purpose, an online survey focusing on pre-travel preparation, knowledge and preventive practices related to travel health was distributed to 324 eligible international students from 14 Thai universities, with the majority being from Asia and Oceania (79.0%; n = 256). The results showed that half of the respondents (53.7%; n = 175) received professional pre-travel advice, mainly because of the mandatory health examination and vaccination requirements of the host university. The study also revealed inadequate knowledge about infectious and non-infectious health risks, with only one-third being aware that Japanese encephalitis is transmitted by mosquito bites, and less than half of the students recognising Thailand's emergency services number. Poor preventive practices were also observed, with less than half of those with new sexual partners consistently using condoms and less than half of those riding motorcycles always wearing helmets. These findings highlight the need for a new strategy to improve the standard of travel health preparation among this group of young adult travellers, particularly those from resource-limited countries.

Single Ad26.COV2.S booster dose following two doses of BBIBP-CorV vaccine against SARS-CoV-2 infection in adults: Day 28 results of a phase 1/2 open-label trial.

BACKGROUND: The inactivated COVID-19 whole-virus vaccine BBIBP-CorV has been extensively used worldwide. Heterologous boosting after primary vaccination can induce higher immune responses against SARS-CoV-2 than homologous boosting. The safety and immunogenicity after 28 days of a single Ad26.COV2.S booster dose given at different intervals after 2 doses of BBIBP-CorV are presented. METHODS: This open-label phase 1/2 trial was conducted in healthy adults in Thailand who had completed 2-dose primary vaccination with BBIBP-CorV. Participants received a single booster dose of Ad26.COV2.S (5 × 1010 virus particles) 90-240 days (Group A1; n = 360) or 45-75 days (Group A2; n = 66) after the second BBIBP-CorV dose. Safety and immunogenicity were assessed over 28 days. Binding IgG antibodies to the full-length pre-fusion Spike and anti-nucleocapsid proteins of SARS-CoV-2 were measured by enzyme-linked immunosorbent assay. The SARS-CoV-2 pseudovirus neutralization assay and live virus microneutralization assay were used to quantify the neutralizing activity of antibodies against ancestral SARS-CoV-2 (Wuhan-Hu-1) and the delta (B.1.617.2) and omicron (B.1.1.529/BA.1 and BA.2) variants. The cell-mediated immune response was measured using a quantitative interferon (IFN)-γ release assay in whole blood. RESULTS: Solicited local and systemic adverse events (AEs) on days 0-7 were mostly mild, as were unsolicited vaccine-related AEs during days 0-28, with no serious AEs. On day 28, anti-Spike binding antibodies increased from baseline by 487- and 146-fold in Groups A1 and A2, and neutralizing antibodies against ancestral SARS-CoV-2 by 55- and 37-fold, respectively. Humoral responses were strongest against ancestral SARS-CoV-2, followed by the delta, then the omicron BA.2 and BA.1 variants. T-cell-produced interferon-γ increased approximately 10-fold in both groups. CONCLUSIONS: A single heterologous Ad26.COV2.S booster dose after two BBIBP-CorV doses was well tolerated and induced robust humoral and cell-mediated immune responses measured at day 28 in both interval groups. CLINICAL TRIALS REGISTRATION: NCT05109559.

Projecting malaria elimination in Thailand using Bayesian hierarchical spatiotemporal models.

Thailand has set a goal of eliminating malaria by 2024 in its national strategic plan. In this study, we used the Thailand malaria surveillance database to develop hierarchical spatiotemporal models to analyze retrospective patterns and predict Plasmodium falciparum and Plasmodium vivax malaria incidences at the provincial level. We first describe the available data, explain the hierarchical spatiotemporal framework underlying the analysis, and then display the results of fitting various space-time formulations to the malaria data with the different model selection metrics. The Bayesian model selection process assessed the sensitivity of different specifications to obtain the optimal models. To assess whether malaria could be eliminated by 2024 per Thailand's National Malaria Elimination Strategy, 2017-2026, we used the best-fitted model to project the estimated cases for 2022-2028. The study results based on the models revealed different predicted estimates between both species. The model for P. falciparum suggested that zero P. falciparum cases might be possible by 2024, in contrast to the model for P. vivax, wherein zero P. vivax cases might not be reached. Innovative approaches in the P. vivax-specific control and elimination plans must be implemented to reach zero P. vivax and consequently declare Thailand as a malaria-free country.

Pneumococcal carriage among high-risk adults in a country with nonmandatory pneumococcal vaccination during the coronavirus disease 2019 pandemic.

BACKGROUND: Streptococcus pneumoniae carriage is a prerequisite for clinical infections and is used to make public health decisions on vaccine licensure. Pneumococcal carriage data among high-risk Thai adults are needed before national vaccine program introduction. The association between coronavirus disease 2019 (COVID-19) and pneumococcal carriage were also investigated. METHODS: During the COVID-19 pandemic, a multi-center cross-sectional study was conducted among high-risk Thai adults from September 2021 to November 2022. Pneumococcal carriage and serotypes were investigated using both conventional and molecular methods. Demographics and co-morbidities were determined for carriage while accounting for case clustering from various study sites. RESULTS: A total of 370 individuals were enrolled. The prevalence of pneumococcal carriage, as determined by the molecular method, was 30.8 % (95 % confidence interval (CI): 26.1-35.8), while after excluding non-typeable pneumococci from the oropharyngeal sample, the carriage prevalence was 20.8 % (95 % CI: 16.79-25.31). The serotype coverage rates by pneumococcal vaccine were 12.3 %, 13.1 %, and 16.4 % for PCV13, PCV15 or PCV20, and PPSV23, respectively, while the non-vaccine type was the majority (45.1 %). The most common serotype was 19B/C (35.5 %), followed by 6 A/B/C/D (10.7 %). The age group under 65 years was associated with a higher pneumococcal carriage rate than the age group 85 and older (odds ratio (OR): 5.01, 95 % CI: 1.75-14.36). There was no significant difference between SARS-CoV-2 and carriage status. CONCLUSIONS: The prevalence of pneumococcal carriage in Thais was high. The majority of serotypes were not covered by the vaccine. Further studies on the link between carriage serotypes and disease are required. The magnitude and serotype distribution of carriage were comparable in the SARS-CoV-2 positive and negative groups.

Diagnostic Performance of Dengue NS1 and Antibodies by Serum Concentration Technique.

Dengue infection has been a public health problem worldwide, especially in tropical areas. A lack of sensitive diagnostic methods in the early phase of the illness is one of the challenging problems in clinical practices. We, herein, analyzed 86 sera of acute febrile patients, from both dengue and non-dengue febrile illness, to study the diagnostic performance of dengue diagnostics. When compared with detection by Polymerase Chain Reaction (PCR), dengue NS1 detection by enzyme-linked immunosorbent assay (ELISA) had the highest sensitivity of 82.4% (with 94.3% specificity), while NS1 by rapid diagnostic test (RDT) had 76.5% sensitivity. IgM detection by ELISA and RDT showed only 27.5% and 17.9% sensitivity, respectively. The combination of NS1 and IgM in RDT yielded a sensitivity of 78.4%, with 97.1% specificity. One of the essential steps in making a diagnosis from patient samples is the preparation process. At present, a variety of techniques have been used to increase the number of analytes in clinical samples. In this study, we focused on the sample concentration method. The sera were concentrated three times with the ultrafiltration method using a 10 kDa molecular weight cut-off membrane. The results showed an increase in the sensitivity of RDT-NS1 detection at 80.4%, with 100% specificity. When combining NS1 and IgM detection, the concentration method granted RDT an 82.4% sensitivity, with 100% specificity. In conclusion, serum concentration by the ultrafiltration method is a simple and applicable technique. It could increase the diagnostic performance of point-of-care dengue diagnostics.

Community acceptability, participation, and adherence to mass drug administration with primaquine for Plasmodium vivax elimination in Southern Thailand: a mixed methods approach.

BACKGROUND: Mass drug administration (MDA) with primaquine (PQ) is being considered for accelerating Plasmodium vivax elimination in remaining active foci. This study aimed to determine the acceptability of MDA with PQ in malaria endemic villages in a malarious setting in the South of Thailand undergoing MDA with PQ. METHODS: A cross-sectional mixed-methods approach was conducted in seven malaria endemic villages where MDA with PQ was implemented. The data were collected from community villagers and health workers using structured questionnaires, in-depth interviews, and focus group discussions. Descriptive statistics and logistic regression models were used for quantitative data analysis. Thematic analysis was applied for qualitative data. RESULTS: Among a total of 469 participants from the MDA villages, 293 participants were eligible for MDA with PQ and 79.86% (234) completed 14-days of PQ. The logistic regressions indicated that males (adjusted odds ratio: 2.52 [95% confidence interval: 1.33-4.81]) and those who are farmers (2.57 [1.12-5.90]) were most likely to participate in the MDA. Among 293 participants in the post-MDA study, 74.06% had originally agreed to participate in the MDA with PQ while 25.94% had originally reported not wanting to participate in the MDA. Of those who originally reported being willing to participate in the MDA, 71.23% followed through with participation in the first or second round. Conversely, 93.24% of those who originally reported not being willing to participate in the MDA did in fact participate in the MDA. Factors contributing to higher odds of agreeing to participate and following through with participation included being male (1.98 [1.06-3.69]) and correctly responding that malaria is preventable (2.32 [1.01-5.35]) with some differences by village. Five key themes emerged from the qualitative analyses: concern about side effects from taking PQ; disbelief that malaria could be eliminated in this setting; low overall concern about malaria infections; misunderstandings about malaria; and a general need to tailor public health efforts for this unique context. CONCLUSION: While the reported likelihood of participating in MDA was high in this setting, actual follow-through was relatively moderate, partially because of eligibility (roughly 71% of those in the follow-up survey who originally agreed to participate actually followed through with participation). One of the largest concerns among study participants was PQ-related side effects-and these concerns likely heavily influenced participant adherence to the MDA. The results of this study can be used to tailor future MDAs, or other public health interventions, in this and potentially other similar settings.

Immunogenicity of a fractional or full third dose of AZD1222 vaccine or BNT162b2 messenger RNA vaccine after two doses of CoronaVac vaccines against the Delta and Omicron variants.

OBJECTIVES: The study aimed to compare the immunogenicity and safety of fractional (half) third doses of heterologous COVID-19 vaccines (AZD1222 or BNT162b2) to full doses after the two-dose CoronaVac and when boosting after three different extended intervals. METHODS: At 60-<90, 90-<120, or 120-180 days intervals after the two-dose CoronaVac, participants were randomized to full-dose or half-dose AZD1222 or BNT162b2, followed up at day 28, 60, and 90. Vaccination-induced immune responses to Ancestral, Delta, and Omicron BA.1 strains were evaluated by antispike, pseudovirus, and microneutralization and T cell assays. Descriptive statistics and noninferiority cut-offs were reported as geometric mean concentration or titer and concentration or titer ratios comparing baseline to day 28 and day 90 and different intervals. RESULTS: No safety concerns were detected. All assays and intervals showed noninferior immunogenicity between full doses and half doses. However, full-dose vaccines and/or longer 120-180-day intervals substantially improved the immunogenicity (measured by antispike or measured by pseudotyped virus neutralizing titers 50; P <0.001). Seroconversion rates were over 90% against the SARS-CoV-2 strains by all assays. Immunogenicity waned more quickly with half doses than full doses but remained high against the Ancestral or Delta strains. Against Omicron, the day 28 immunogenicity increased with longer intervals than shorter intervals for full-dose vaccines. CONCLUSION: Immune responses after day 28 when boosting at longer intervals after the two-dose CoronaVac was optimal. Half doses met the noninferiority criteria compared with the full dose by all the immune assays assessed.

Characteristics of Drug-induced Liver Injury in Chronic Liver Disease: Results from the Thai Association for the Study of the Liver (THASL) DILI Registry.

Background and Aims: The impact of drug-induced liver injury (DILI) on patients with chronic liver disease (CLD) is unclear. There are few reports comparing DILI in CLD and non-CLD patients. In this study, we aimed to determine the incidence and outcomes of DILI in patients with and without CLD. Methods: We collected data on eligible individuals with suspected DILI between 2018 and 2020 who were evaluated systematically for other etiologies, causes, and the severity of DILI. We compared the causative agents, clinical features, and outcomes of DILI among subjects with and without CLD who were enrolled in the Thai Association for the Study of the Liver DILI registry. Subjects with definite, or highly likely DILI were included in the analysis. Results: A total of 200 subjects diagnosed with DILI were found in the registry. Of those, 41 had CLD and 159 had no evidence of CLD in their background. Complementary and alternative medicine (CAM) products were identified as the most common class of DILI agents. Approximately 59% of DILI in the CLD and 40% in non-CLD group were associated with CAM use. Individuals with pre-existing CLD had similar severity including mortality. Twelve patients (6%) developed adverse outcomes related to DILI including seven (3.5%) deaths and five (2.5%) with liver failure. Mortality was 4.88% in CLD and 3.14% in non-CLD subjects over median periods of 58 (8-106) days and 22 (1-65) days, respectively. Conclusions: In this liver disease registry, the causes, clinical presentation, and outcomes of DILI in subjects with CLD and without CLD patients were not different. Further study is required to confirm our findings.

Molecular markers of dihydroartemisinin-piperaquine resistance in northwestern Thailand.

BACKGROUND: Dihydroartemisinin-piperaquine (DHA-PPQ) combination therapy is the current first-line treatment for Plasmodium falciparum malaria in Thailand. Since its introduction in 2015, resistance to this drug combination has emerged in the eastern part of the Greater Mekong Subregion including the eastern part of Thailand near Cambodia. This study aimed to assess whether the resistance genotypes have arisen the western part of country. METHODS: Fifty-seven P. falciparum-infected blood samples were collected in Tak province of northwestern Thailand between 2013 and 2019. Resistance to DHA was examined through the single nucleotide polymorphisms (SNPs) of kelch13. PPQ resistance was examined through the copy number plasmepsin-2 and the SNPs of Pfcrt. RESULTS: Among the samples whose kelch13 were successfully sequenced, approximately half (31/55; 56%) had mutation associated with artemisinin resistance, including G533S (23/55; 42%), C580Y (6/55; 11%), and G538V (2/55; 4%). During the study period, G533S mutation appeared and increased from 20% (4/20) in 2014 to 100% (9/9) in 2019. No plasmepsin-2 gene amplification was observed, but one sample (1/54) had the Pfcrt F145I mutation previously implicated in PPQ resistance. CONCLUSIONS: Kelch13 mutation was common in Tak Province in 2013-2019. A new mutation G533S emerged in 2014 and rose to dominance in 2019. PPQ resistance marker Pfcrt F145I was also detected in 2019. Continued surveillance of treatment efficacy and drug resistance markers is warranted.

Multidisciplinary Investigations of Sustained Malaria Transmission in the Greater Mekong Subregion.

In the course of malaria elimination in the Greater Mekong Subregion (GMS), malaria epidemiology has experienced drastic spatiotemporal changes with residual transmission concentrated along international borders and the rising predominance of Plasmodium vivax. The emergence of Plasmodium falciparum parasites resistant to artemisinin and partner drugs renders artemisinin-based combination therapies less effective while the potential spread of multidrug-resistant parasites elicits concern. Vector behavioral changes and insecticide resistance have reduced the effectiveness of core vector control measures. In recognition of these problems, the Southeast Asian International Center of Excellence for Malaria Research (ICEMR) has been conducting multidisciplinary research to determine how human migration, antimalarial drug resistance, vector behavior, and insecticide resistance sustain malaria transmission at international borders. These efforts allow us to comprehensively understand the ecology of border malaria transmission and develop population genomics tools to identify and track parasite introduction. In addition to employing in vivo, in vitro, and molecular approaches to monitor the emergence and spread of drug-resistant parasites, we also use genomic and genetic methods to reveal novel mechanisms of antimalarial drug resistance of parasites. We also use omics and population genetics approaches to study insecticide resistance in malaria vectors and identify changes in mosquito community structure, vectorial potential, and seasonal dynamics. Collectively, the scientific findings from the ICEMR research activities offer a systematic view of the factors sustaining residual malaria transmission and identify potential solutions to these problems to accelerate malaria elimination in the GMS.