Temporal changes in SARS-CoV-2 clearance kinetics and the optimal design of antiviral pharmacodynamic studies: an individual patient data meta-analysis of a randomised, controlled, adaptive platform study (PLATCOV).

BACKGROUND: Effective antiviral drugs prevent hospitalisation and death from COVID-19. Antiviral efficacy can be efficiently assessed in vivo by measuring rates of SARS-CoV-2 clearance estimated from serial viral genome densities quantitated in nasopharyngeal or oropharyngeal swab eluates. We conducted an individual patient data meta-analysis of unblinded arms in the PLATCOV platform trial to characterise changes in viral clearance kinetics and infer optimal design and interpretation of antiviral pharmacometric evaluations. METHODS: Serial viral density data were analysed from symptomatic, previously healthy, adult patients (within 4 days of symptom onset) enrolled in a large multicentre, randomised, adaptive, pharmacodynamic, platform trial (PLATCOV) comparing antiviral interventions for SARS-CoV-2. Viral clearance rates over 1 week were estimated under a hierarchical Bayesian linear model with B-splines used to characterise temporal changes in enrolment viral densities and clearance rates. Bootstrap re-sampling was used to assess the optimal duration of follow-up for pharmacometric assessment, where optimal was defined as maximising the expected Z score when comparing effective antivirals with no treatment. PLATCOV is registered at ClinicalTrials.gov, NCT05041907. FINDINGS: Between Sept 29, 2021, and Oct 20, 2023, 1262 patients were randomly assigned in the PLATCOV trial. Unblinded data were available from 800 patients (who provided 16 818 oropharyngeal viral quantitative PCR [qPCR] measurements), of whom 504 (63%) were female. 783 (98%) patients had received at least one vaccine dose and 703 (88%) were fully vaccinated. SARS-CoV-2 viral clearance was biphasic (bi-exponential). The first phase (α) was accelerated by effective interventions. For all the effective interventions studied, maximum discriminative power (maximum expected Z score) was obtained when evaluating serial data from the first 5 days after enrolment. Over the 2-year period studied, median viral clearance half-lives estimated over 7 days shortened from 16·6 h (IQR 15·3 to 18·2) in September, 2021, to 9·2 h (8·0 to 10·6) in October, 2023, in patients receiving no antiviral drugs, equivalent to a relative reduction of 44% (95% credible interval [CrI] 19 to 64). A parallel reduction in viral clearance half-lives over time was observed in patients receiving antiviral drugs. For example, in the 158 patients assigned to ritonavir-boosted nirmatrelvir (3380 qPCR measurements), the median viral clearance half-life reduced from 6·4 h (IQR 5·7 to 7·3) in June, 2022, to 4·8 h (4·2 to 5·5) in October, 2023, a relative reduction of 26% (95% CrI -4 to 42). INTERPRETATION: SARS-CoV-2 viral clearance kinetics in symptomatic, vaccinated individuals accelerated substantially over 2 years of the pandemic, necessitating a change to how new SARS-CoV-2 antivirals are compared (ie, shortening the period of pharmacodynamic assessment). As of writing (October, 2023), antiviral efficacy in COVID-19 can be efficiently assessed in vivo using serial qPCRs from duplicate oropharyngeal swab eluates taken daily for 5 days after drug administration. FUNDING: Wellcome Trust.

Barriers and enablers to blood culture sampling in Indonesia, Thailand and Viet Nam: a Theoretical Domains Framework-based survey.

OBJECTIVE: Blood culture (BC) sampling is recommended for all suspected sepsis patients prior to antibiotic administration. We examine barriers and enablers to BC sampling in three Southeast Asian countries. DESIGN: A Theoretical Domains Framework (TDF)-based survey, comprising a case scenario of a patient presenting with community-acquired sepsis and all 14 TDF domains of barriers/enablers to BC sampling. SETTING: Hospitals in Indonesia, Thailand and Viet Nam, December 2021 to 30 April 2022. PARTICIPANTS: 1070 medical doctors and 238 final-year medical students were participated in this study. Half of the respondents were women (n=680, 52%) and most worked in governmental hospitals (n=980, 75.4%). OUTCOME MEASURES: Barriers and enablers to BC sampling. RESULTS: The proportion of respondents who answered that they would definitely take BC in the case scenario was highest at 89.8% (273/304) in Thailand, followed by 50.5% (252/499) in Viet Nam and 31.3% (157/501) in Indonesia (p<0.001). Barriers/enablers in nine TDF domains were considered key in influencing BC sampling, including 'priority of BC (TDF-goals)', 'perception about their role to order or initiate an order for BC (TDF-social professional role and identity)', 'perception that BC is helpful (TDF-beliefs about consequences)', 'intention to follow guidelines (TDF-intention)', 'awareness of guidelines (TDF-knowledge)', 'norms of BC sampling (TDF-social influence)', 'consequences that discourage BC sampling (TDF-reinforcement)', 'perceived cost-effectiveness of BC (TDF-environmental context and resources)' and 'regulation on cost reimbursement (TDF-behavioural regulation)'. There was substantial heterogeneity between the countries. In most domains, the lower (higher) proportion of Thai respondents experienced the barriers (enablers) compared with that of Indonesian and Vietnamese respondents. A range of suggested intervention types and policy options was identified. CONCLUSIONS: Barriers and enablers to BC sampling are varied and heterogenous. Cost-related barriers are more common in more resource-limited countries, while many barriers are not directly related to cost. Context-specific multifaceted interventions at both hospital and policy levels are required to improve diagnostic stewardship practices.

Seroprevalence of dengue, Japanese encephalitis and Zika among long-term expatriates in Thailand.

BACKGROUND: Travel to Southeast Asia increases the likelihood of acquiring mosquito-borne Flavivirus infections such as dengue (DENV), Japanese encephalitis (JEV) and Zika viruses (ZIKV). Expatriates are long-term travellers who have a higher risk of mosquito-borne illness at their destination country. The purpose of this study was to evaluate the seroprevalence of DENV, JEV and ZIKV infections and the determinants contributing to seropositivity among expatriates living in Thailand. METHODS: A cross-sectional study was performed from December 2017 to February 2020. Expatriates from non-Flavivirus endemic countries were recruited. 5 mL of blood was collected for DENV 1-4, JEV and ZIKV antibody testing by plaque reduction neutralization test (PRNT50). Individuals with vaccination histories or diagnoses for dengue, Japanese encephalitis, yellow fever and tick-borne encephalitis were excluded. RESULTS: Among 254 participants, most participants (83.1%) were male, the mean age was 65 years and the median duration of stay in Thailand was 6 years. Seroprevalence rate of any Flavivirus, non-specific DENV, DENV1-4, JEV and ZIKV were 34.3, 30.7, 20.5, 18.1, 18.9, 10.6, 4.7 and 2.8%, respectively. The presence of neutralizing antibodies against DENV1-4 positively correlates with the duration of stay in Thailand. DENV seropositivity was associated with living in urban areas (aOR 2.75, 95% CI 1.36-5.57). Expatriates were unlikely to have detectable anti-JEV antibodies regardless of time spent in a JEV-endemic area. No risk factors were identified that were significantly associated with JEV or ZIKV seropositivity. Only 48.4% received pre-travel counselling services, while only 18.9% visited a travel medicine specialist. CONCLUSIONS: A high proportion (34.3%) of long-term expatriates living in Thailand were seropositive for flavivirus, mainly from dengue (30.7%). To minimize risk, travel medicine practitioners should provide adequate pre-travel health risk information on mosquito-borne flavivirus infection and offer advice on mosquito bite prevention strategies. Dengue vaccine might be considered in high-risk travellers such as long-term expatriate.

Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial.

In early symptomatic COVID-19 treatment, high dose oral favipiravir did not accelerate viral clearance. BACKGROUND: Favipiravir, an anti-influenza drug, has in vitro antiviral activity against SARS-CoV-2. Clinical trial evidence to date is inconclusive. Favipiravir has been recommended for the treatment of COVID-19 in some countries. METHODS: In a multicentre open-label, randomised, controlled, adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomised to one of ten treatment arms including high dose oral favipiravir (3.6g on day 0 followed by 1.6g daily to complete 7 days treatment) or no study drug. The primary outcome was the rate of viral clearance (derived under a linear mixed-effects model from the daily log10 viral densities in standardised duplicate oropharyngeal swab eluates taken daily over 8 days [18 swabs per patient]), assessed in a modified intention-to-treat population (mITT). The safety population included all patients who received at least one dose of the allocated intervention. This ongoing adaptive platform trial was registered at ClinicalTrials.gov (NCT05041907) on 13/09/2021. RESULTS: In the final analysis, the mITT population contained data from 114 patients randomised to favipiravir and 126 patients randomised concurrently to no study drug. Under the linear mixed-effects model fitted to all oropharyngeal viral density estimates in the first 8 days from randomisation (4,318 swabs), there was no difference in the rate of viral clearance between patients given favipiravir and patients receiving no study drug; a -1% (95% credible interval: -14 to 14%) difference. High dose favipiravir was well-tolerated. INTERPRETATION: Favipiravir does not accelerate viral clearance in early symptomatic COVID-19. The viral clearance rate estimated from quantitative measurements of oropharyngeal eluate viral densities assesses the antiviral efficacy of drugs in vivo with comparatively few studied patients.

Antiviral efficacy of molnupiravir versus ritonavir-boosted nirmatrelvir in patients with early symptomatic COVID-19 (PLATCOV): an open-label, phase 2, randomised, controlled, adaptive trial.

BACKGROUND: Molnupiravir and ritonavir-boosted nirmatrelvir are the two leading oral COVID-19 antiviral treatments, but their antiviral activities in patients have not been compared directly. The aim of this ongoing platform trial is to compare different antiviral treatments using the rate of viral clearance as the measure of antiviral effect. METHODS: PLATCOV is an open-label, multicentre, phase 2, randomised, controlled, adaptive pharmacometric platform trial running in Thailand, Brazil, Pakistan, and Laos. The component of the trial reported here was conducted in the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. We recruited low-risk adult patients aged 18-50 years with early symptomatic COVID-19 (<4 days of symptoms). Eligible patients were randomly assigned using block randomisation via a centralised web app to one of seven treatment groups: molnupiravir, ritonavir-boosted nirmatrelvir, casirivimab-imdevimab, tixagevimab-cilgavimab, favipiravir, fluoxetine, or no study drug. The no study drug group comprised a minimum proportion of 20% of patients at all times, with uniform randomisation ratios applied across the active treatment groups. Results for the concurrently randomised molnupiravir, ritonavir-boosted nirmatrelvir, and no study drug groups are reported here. The primary endpoint was the rate of oropharyngeal viral clearance assessed in a modified intention-to-treat population, defined as patients with more than 2 days of follow-up. Safety was assessed in all participants who took at least one dose of the medication. The viral clearance rate was derived under a Bayesian hierarchical linear model fitted to the log10 viral densities in standardised duplicate oropharyngeal swab eluates taken daily over 1 week (18 measurements). Treatment groups with a probability of more than 0·9 that viral clearance was accelerated by more than 20% compared with no drug entered a non-inferiority comparison (with a 10% non-inferiority margin) compared with the platform's current most effective drug. This ongoing trial is registered at ClinicalTrials.gov, NCT05041907. FINDINGS: Between June 6, 2022, and Feb 23, 2023, 209 patients in Thailand were enrolled and concurrently randomly assigned to molnupiravir (n=65), ritonavir-boosted nirmatrelvir (n=59), or no study drug (n=85). 129 (62%) of the patients were female and 80 (38%) were male. Relative to the no study drug group, the rates of viral clearance were 37% (95% credible interval 16-65) faster with molnupiravir and 84% (54-119) faster with ritonavir-boosted nirmatrelvir. In the non-inferiority comparison, viral clearance was 25% (10-38) slower with molnupiravir than ritonavir-boosted nirmatrelvir. Molnupiravir was removed from the study platform when it reached the prespecified inferiority margin of 10% compared with ritonavir-boosted nirmatrelvir. Median estimated viral clearance half-lives were 8·5 h (IQR 6·7-10·1) with ritonavir-boosted nirmatrelvir, 11·6 h (8·6-15·4) with molnupiravir, and 15·5 h (11·9-21·2) with no study drug. Viral rebound occurred more frequently following nirmatrelvir (six [10%] of 58) compared with the no study drug (one [1%] of 84; p=0·018) or the molnupiravir (one [2%] of 65; p=0·051) groups. Persistent infections following molnupiravir had more viral mutations (three of nine patients had an increased number of single nucleotide polymorphisms in samples collected at 7 or more days compared with those at baseline) than after nirmatrelvir (zero of three) or no study drug (zero of 19). There were no adverse events of grade 3 or worse, or serious adverse events in any of the reported treatment groups. INTERPRETATION: Both molnupiravir and ritonavir-boosted nirmatrelvir accelerate oropharyngeal SARS-CoV-2 viral clearance in patients with COVID-19, but the antiviral effect of ritonavir-boosted nirmatrelvir was substantially greater. Measurement of oropharyngeal viral clearance rates provides a rapid and well tolerated approach to the assessment and comparison of antiviral drugs in patients with COVID-19. It should be evaluated in other acute viral respiratory infections. FUNDING: Wellcome Trust through the COVID-19 Therapeutics Accelerator.

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.

Clinical Antiviral Efficacy of Remdesivir in Coronavirus Disease 2019: An Open-Label, Randomized Controlled Adaptive Platform Trial (PLATCOV).

BACKGROUND: Uncertainty over the therapeutic benefit of parenteral remdesivir in coronavirus disease 2019 (COVID-19) has resulted in varying treatment guidelines. METHODS: In a multicenter open-label, controlled, adaptive, pharmacometric platform trial, low-risk adult patients with early symptomatic COVID-19 were randomized to 1 of 8 treatment arms including intravenous remdesivir (200 mg followed by 100 mg daily for 5 days) or no study drug. The primary outcome was the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance (estimated under a linear model fit to the daily log10 viral densities, days 0-7) in standardized duplicate oropharyngeal swab eluates, in a modified intention-to-treat population. This ongoing adaptive trial is registered at ClinicalTrials.gov (NCT05041907). RESULTS: The 2 study arms enrolled 131 patients (remdesivir n = 67, no study drug n = 64) and estimated viral clearance rates from a median of 18 swab samples per patient (a total of 2356 quantitative polymerase chain reactions). Under the linear model, compared with the contemporaneous control arm (no study drug), remdesivir accelerated mean estimated viral clearance by 42% (95% credible interval, 18%-73%). CONCLUSIONS: Parenteral remdesivir accelerates viral clearance in early symptomatic COVID-19. Pharmacometric assessment of therapeutics using the method described can determine in vivo clinical antiviral efficacy rapidly and efficiently.

Pharmacometrics of high-dose ivermectin in early COVID-19 from an open label, randomized, controlled adaptive platform trial (PLATCOV).

Background: There is no generally accepted methodology for in vivo assessment of antiviral activity in SARS-CoV-2 infections. Ivermectin has been recommended widely as a treatment of COVID-19, but whether it has clinically significant antiviral activity in vivo is uncertain. Methods: In a multicentre open label, randomized, controlled adaptive platform trial, adult patients with early symptomatic COVID-19 were randomized to one of six treatment arms including high-dose oral ivermectin (600 µg/kg daily for 7 days), the monoclonal antibodies casirivimab and imdevimab (600 mg/600 mg), and no study drug. The primary outcome was the comparison of viral clearance rates in the modified intention-to-treat population. This was derived from daily log10 viral densities in standardized duplicate oropharyngeal swab eluates. This ongoing trial is registered at https://clinicaltrials.gov/ (NCT05041907). Results: Randomization to the ivermectin arm was stopped after enrolling 205 patients into all arms, as the prespecified futility threshold was reached. Following ivermectin, the mean estimated rate of SARS-CoV-2 viral clearance was 9.1% slower (95% confidence interval [CI] -27.2% to +11.8%; n=45) than in the no drug arm (n=41), whereas in a preliminary analysis of the casirivimab/imdevimab arm it was 52.3% faster (95% CI +7.0% to +115.1%; n=10 (Delta variant) vs. n=41). Conclusions: High-dose ivermectin did not have measurable antiviral activity in early symptomatic COVID-19. Pharmacometric evaluation of viral clearance rate from frequent serial oropharyngeal qPCR viral density estimates is a highly efficient and well-tolerated method of assessing SARS-CoV-2 antiviral therapeutics in vitro. Funding: 'Finding treatments for COVID-19: A phase 2 multi-centre adaptive platform trial to assess antiviral pharmacodynamics in early symptomatic COVID-19 (PLAT-COV)' is supported by the Wellcome Trust Grant ref: 223195/Z/21/Z through the COVID-19 Therapeutics Accelerator. Clinical trial number: NCT05041907.

Healthcare seeking during travel: an analysis by the GeoSentinel surveillance network of travel medicine providers.

BACKGROUND: International travellers may seek care abroad to address health problems that arise during their trip or plan healthcare outside their country of residence as medical tourists. METHODS: Data were collected on travellers evaluated at GeoSentinel Network sites who reported healthcare during travel. Both unplanned and planned healthcare were analysed, including the reason and nature of healthcare sought, characteristics of the treatment provided and outcomes. Travellers that presented for rabies post-exposure prophylaxis were described elsewhere and were excluded from detailed analysis. RESULTS: From May 2017 through June 2020, after excluding travellers obtaining rabies post-exposure prophylaxis (n= 415), 1093 travellers reported care for a medical or dental issue that was an unanticipated part of the travellers' planned itinerary (unplanned healthcare). Travellers who sought unplanned healthcare abroad had frequent diagnoses of acute diarrhoea, dengue, falciparum malaria and unspecified viral syndrome, and obtained care in 131 countries. Thirty-four (3%) reported subsequent deterioration and 230 (21%) reported no change in condition; a third (n = 405; 37%) had a pre-travel health encounter. Forty-one travellers had sufficient data on planned healthcare abroad for analysis. The most common destinations were the US, France, Dominican Republic, Belgium and Mexico. The top reasons for their planned healthcare abroad were unavailability of procedure at home (n = 9; 19%), expertise abroad (n = 9; 19%), lower cost (n = 8; 17%) and convenience (n = 7; 15%); a third (n = 13; 32%) reported cosmetic or surgical procedures. Early and late complications occurred in 14 (33%) and 4 (10%) travellers, respectively. Four travellers (10%) had a pre-travel health encounter. CONCLUSIONS: International travellers encounter health problems during travel that often could be prevented by pre-travel consultation. Travellers obtaining planned healthcare abroad can experience negative health consequences associated with treatments abroad, for which pre-travel consultations could provide advice and potentially help to prevent complications.

Dynamics of Different Classes and Subclasses of Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 Variants after Coronavirus Disease 2019 and CoronaVac Vaccination in Thailand.

The humoral immune response plays a key role in protecting the population from SARS-CoV-2 transmission. Patients who recovered from COVID-19 as well as fully vaccinated individuals have elevated levels of antibodies. The dynamic levels of the classes and subclasses of antibody responses to new variants that occur in different populations remain unclear. We prospectively recruited 60 participants, including COVID-19 patients and CoronaVac-vaccinated individuals, in Thailand from May to August 2021. Plasma samples were collected on day 0, day 14, and day 28 to determine the dynamic levels of the classes and subclasses of plasma antibodies against the receptor-binding domain (RBD) in the spike protein (S) of four SARS-CoV-2 strains (Wuhan, Alpha, Delta, and Omicron) via enzyme-linked immunosorbent assay. Our results indicated that the patients with SARS-CoV-2 infections had broader class and subclass profiles as well as higher levels of anti-S RBD antibodies to the Wuhan, Alpha, and Delta strains than did the CoronaVac-vaccinated individuals. The median antibody levels increased and subsequently declined in a month in the COVID-19 patients and in the vaccinated group. Correlations of the classes and subclasses of antibodies were observed in the COVID-19 patients but not in the vaccinated individuals. The levels of all of the anti-S RBD antibodies against the Omicron variant were low in the patients and in the vaccinated individuals. Our study revealed distinct antibody profiles between the two cohorts, suggesting different pathways of immune activation. This could have an impact on protection from infections by new variants of concern (VOC). IMPORTANCE The antibody responses to new SARS-CoV-2 variants that occur in different populations remain unclear. In this study, we recruited 60 participants, including COVID-19 patients and CoronaVac-vaccinated individuals, in Thailand and determined the dynamic levels of the IgG, IgA, IgM, and IgG subclasses of antibodies against the spike protein (S) of four SARS-CoV-2 strains. Our results showed that the patients with SARS-CoV-2 infections had broader profiles and higher levels of antibodies to the Wuhan, Alpha, and Delta strains than did the CoronaVac-vaccinated individuals. The antibody levels of both groups increased and subsequently decreased within 1 month. Higher and functional correlations of these antibodies were observed in the COVID-19 patients. The levels of all anti-S RBD antibodies against the Omicron variant were low in patients and vaccinated individuals. Our study revealed distinct antibody responses between the two groups, suggesting different pathways of immune response, which may have an impact on protection from infections by new SARS-CoV-2 variants.

Temporal Trend of COVID-19 Vaccine Acceptance and Factors Influencing International Travellers.

The COVID-19 pandemic has seen disrupted international travel due to travel restrictions and public health measures aimed at containing the spread of the virus. With increasing evidence of the COVID-19 vaccines' ability to mitigate disease severity, reopening tourism is desirable to promote the recovery of the global economy. However, the COVID-19 vaccine and vaccination passport for international travellers remains an ongoing debate. Little is known of the acceptance of these and the influencing factors among this population group. Therefore, this study sought to determine the temporal trend in COVID-19 vaccine acceptance and influencing factors among international travellers. A cross-sectional study was conducted using a self-administered questionnaire among international travellers who visited the Thai Travel Clinic, Hospital for Tropical Diseases, Mahidol University, Thailand from June 2021 to December 2021 (3 different variants dominated during this period). Study data were analyzed using SPSS software, version 23. Chi-square was used to demonstrate associations. Binary logistic regression was used to evaluate the magnitude of effect, demonstrated by odds ratio with 95% confidence interval. All significant variables were included in a multinomial logistic regression model to estimate adjusted odds ratios. The study enrolled 1068 travellers, 719 (67.3%) Thai and 349 (32.7%) foreign travellers. Most travellers were female (55.4%) and aged 18-30 years. The three main purposes for visiting the clinic were: for study, visiting friends and relatives, and returning to their home country. The overall COVID-19 vaccine acceptance rate among the travellers was 96.2%. The temporal trend of acceptance among Thai and non-Thai travelers varied from 93-99% and 93-100%, respectively. Vaccine efficacy, protective duration of the vaccine, risk of infection, and travel plan were factors strongly associated with COVID-19 vaccine acceptance. In conclusion, the COVID-19 vaccine acceptance rate among these international travellers was very high. The safe and effective reopening of tourism to international travellers will facilitate economic recovery.

Cardiovascular Manifestation of the BNT162b2 mRNA COVID-19 Vaccine in Adolescents.

This study focuses on cardiovascular manifestation, particularly myocarditis and pericarditis events, after BNT162b2 mRNA COVID-19 vaccine injection in Thai adolescents. This prospective cohort study enrolled students aged 13-18 years from two schools, who received the second dose of the BNT162b2 mRNA COVID-19 vaccine. Data including demographics, symptoms, vital signs, ECG, echocardiography, and cardiac enzymes were collected at baseline, Day 3, Day 7, and Day 14 (optional) using case record forms. We enrolled 314 participants; of these, 13 participants were lost to follow-up, leaving 301 participants for analysis. The most common cardiovascular signs and symptoms were tachycardia (7.64%), shortness of breath (6.64%), palpitation (4.32%), chest pain (4.32%), and hypertension (3.99%). One participant could have more than one sign and/or symptom. Seven participants (2.33%) exhibited at least one elevated cardiac biomarker or positive lab assessments. Cardiovascular manifestations were found in 29.24% of patients, ranging from tachycardia or palpitation to myopericarditis. Myopericarditis was confirmed in one patient after vaccination. Two patients had suspected pericarditis and four patients had suspected subclinical myocarditis. In conclusion, Cardiovascular manifestation in adolescents after BNT162b2 mRNA COVID-19 vaccination included tachycardia, palpitation, and myopericarditis. The clinical presentation of myopericarditis after vaccination was usually mild and temporary, with all cases fully recovering within 14 days. Hence, adolescents receiving mRNA vaccines should be monitored for cardiovascular side effects. Clinical Trial Registration: NCT05288231.

Cross-platform mobile app development for disseminating public health information to travelers in Thailand: development and usability.

BACKGROUND: The risk of disease is a key factor that travelers have identified when planning to travel abroad, as many people are concerned about getting sick. Mobile devices can be an effective means for travelers to access information regarding disease prevalence in their planned destinations, potentially reducing the risk of exposure. METHODS: We developed a mobile app, ThaiEpidemics, using cross-platform technology to provide information about disease prevalence and status for travelers to Thailand. We aimed to assess the app's usability in terms of engagement, search logs, and effectiveness among target users. The app was developed using the principle of mobile application development life cycle, for both iOS and Android. As its data source, the app used weekly data from national disease-surveillance reports. We conduced our study among visitors to the Travel Clinic in the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. The participants were informed that the app would collect usage and search logs related to their queries. After the second log-in, the app prompted participants to complete an e-survey regarding their opinions and preferences related to their awareness of disease prevalence and status. RESULTS: We based our prototype of ThaiEpidemics on a conceptualized framework for visualizing the distribution of 14 major diseases of concern to tourists in Southeast Asia. The app provided users with functions and features to search for and visualize disease prevalence and status in Thailand. The participants could access information for their current location and elsewhere in the country. In all, 83 people installed the app, and 52 responded to the e-survey. Regardless of age, education, and continent of origin, almost all e-survey respondents believed the app had raised their awareness of disease prevalence and status when travelling. Most participants searched for information for all 14 diseases; some searched for information specifically about dengue and malaria. CONCLUSIONS: ThaiEpidemics is evidently potentially useful for travelers. Should the app be adopted for use by travelers to Thailand, it could have an impact on wider knowledge distribution, which might result in decreased exposure, increased prophylaxis, and therefore a potential decreased burden on the healthcare system. For app developers who are developing/implementing this kind of app, it is important to address standardization of the data source and users' concerns about the confidentiality and safety of their mobile devices.

Adherence and Health Problems in Thai Travellers Living with HIV.

It is important to focus on adherence to antiretroviral therapy (ART) and health problems of travellers living with HIV (TLWHIV) during travel. This study was conducted to investigate factors related to adherence and health problems among TLWHIV. This multicentre, cross-sectional observational study was conducted among TLWHIV in university hospitals from August 2019 to July 2020. Factors associated with adherence to ART were evaluated using a logistic regression model. Health problems and risk exposure were also examined among participants during travel. Of 321 TLWHIV, 20 (6.23%) showed moderate-to-poor adherence, among whom 3 (15%) had viral rebound after travelling. Travellers frequently missed ART during the first 3 days of their trip. International destination was associated with moderate-to-poor adherence. In total, 237 (73.8%) travellers reported health problems during travel, among whom 36 required medical attention. Sexual or sharp exposure was found in <5% of travellers during travel. Approximately 95% of Thai TLWHIV had good ART adherence. International destination was the major factor determining adherence. TLWHIV should be encouraged to seek pretravel consultation. Healthcare providers should discuss health risk prevention and teach about ART dosing during travel to enhance adherence and minimise toxicity.

False Positivity of Anti-SARS-CoV-2 Antibodies in Patients with Acute Tropical Diseases in Thailand.

Serology remains a useful indirect method of diagnosing tropical diseases, especially in dengue infection. However, the current literature regarding cross-reactivity between SARS-CoV-2 and dengue serology is limited and revealed conflicting results. As a means to uncover relevant serological insight involving antibody classes against SARS-CoV-2 and cross-reactivity, anti-SARS-CoV-2 IgA, IgM, and IgG ELISA, based on spike and nucleocapsid proteins, were selected for a fever-presenting tropical disease patient investigation. The study was conducted at the Faculty of Tropical Medicine during March to December 2021. The study data source comprised (i) 170 non-COVID-19 sera from 140 adults and children presenting with acute undifferentiated febrile illness and 30 healthy volunteers, and (ii) 31 COVID-19 sera from 17 RT-PCR-confirmed COVID-19 patients. Among 170 non-COVID-19 samples, 27 were false positives (15.9%), of which IgA, IgM, and IgG cross-reactive antibody classes were detected in 18 (10.6%), 9 (5.3%), and 3 (1.8%) cases, respectively. Interestingly, one case exhibited both IgA and IgM false positivity, while two cases exhibited both IgA and IgG false positivity. The false positivity rate in anti-SARS-CoV-2 IgA and IgM was reported in adults with dengue infection (11.3% and 5%) and adults with other tropical diseases (16.7% and 13.3%). The urea dissociation method applied to mitigate false positivity resulted in significantly decreased ELISA-based false and true positives. In conclusion, the analysis of antibody against SARS-CoV-2 in sera of patients with different tropical diseases showed that high IgA and IgM false positivity thus potentially limits serological assay utility in fever-presenting patients in tropical areas.

Trend Analysis of Travel Medicine Topics Presented at an International Tropical Medicine Conference.

Prior to the COVID-19 pandemic, there was a rapid increase in international travel. Travel medicine is a branch of preventive medicine focusing on risk assessment pre-travel, during travel and post-travel with the aim of promoting health and preventing adverse health outcomes. Travel medicine specialists inform travelers about potential health risks and mitigate infectious disease risks such as travelers' diarrhea, yellow fever, and malaria. Travel medicine topics were popular in the American Society of Tropical Medicine and Hygiene conferences between 2016 and 2020, and now comprise approximately 2% of all presentations. Most topics related to the post-travel assessment (50%), followed by diseases contracted during travel (26%), and pre-travel assessment and consultation (24%). Our analysis of the 10 sub-domains of travel medicine issues found that malaria (26%) and immunization (12%) were represented to the greatest extent. We anticipate that both travel and tropical medicine fields will regain their popularity after recovery from the pandemic.