Durability of the Effectiveness of Heterologous COVID-19 Vaccine Regimens in Thailand: Retrospective Cohort Study Using National Registration Data.

BACKGROUND: The durability of heterologous COVID-19 vaccine effectiveness (VE) has been primarily studied in high-income countries, while evaluation of heterologous vaccine policies in low- and middle-income countries remains limited. OBJECTIVE: We aimed to evaluate the duration during which the VE of heterologous COVID-19 vaccine regimens in mitigating serious outcomes, specifically severe COVID-19 and death following hospitalization with COVID-19, remains over 50%. METHODS: We formed a dynamic cohort by linking records of Thai citizens aged ≥18 years from citizen vital, COVID-19 vaccine, and COVID-19 cases registry databases between May 2021 and July 2022. Encrypted citizen identification numbers were used to merge the data between the databases. This study focuses on 8 common heterologous vaccine sequences: CoronaVac/ChAdOx1, ChAdOx1/BNT162b2, CoronaVac/CoronaVac/ChAdOx1, CoronaVac/ChAdOx1/ChAdOx1, CoronaVac/ChAdOx1/BNT162b2, BBIBP-CorV/BBIBP-CorV/BNT162b2, ChAdOx1/ChAdOx1/BNT162b2, and ChAdOx1/ChAdOx1/mRNA-1273. Nonimmunized individuals were considered for comparisons. The cohort was stratified according to the vaccination status, age, sex, province location, month of vaccination, and outcome. Data analysis employed logistic regression to determine the VE, accounting for potential confounders and durability over time, with data observed over a follow-up period of 7 months. RESULTS: This study includes 52,580,841 individuals, with approximately 17,907,215 and 17,190,975 receiving 2- and 3-dose common heterologous vaccines (not mutually exclusive), respectively. The 2-dose heterologous vaccinations offered approximately 50% VE against severe COVID-19 and death following hospitalization with COVID-19 for 2 months; however, the protection significantly declined over time. The 3-dose heterologous vaccinations sustained over 50% VE against both outcomes for at least 8 months, as determined by logistic regression with durability time-interaction modeling. The vaccine sequence consisting of CoronaVac/CoronaVac/ChAdOx1 demonstrated >80% VE against both outcomes, with no evidence of VE waning. The final monthly measured VE of CoronaVac/CoronaVac/ChAdOx1 against severe COVID-19 and death following hospitalization at 7 months after the last dose was 82% (95% CI 80.3%-84%) and 86.3% (95% CI 83.6%-84%), respectively. CONCLUSIONS: In Thailand, within a 7-month observation period, the 2-dose regimens could not maintain a 50% VE against severe and fatal COVID-19 for over 2 months, but all of the 3-dose regimens did. The CoronaVac/CoronaVac/ChAdOx1 regimen showed the best protective effect against severe and fatal COVID-19. The estimated durability of 50% VE for at least 8 months across all 3-dose heterologous COVID-19 vaccine regimens supports the adoption of heterologous prime-boost vaccination strategies, with a primary series of inactivated virus vaccine and boosting with either a viral vector or an mRNA vaccine, to prevent similar pandemics in low- and middle-income countries.

Incidence rates of myocarditis and pericarditis within 30 days following homologous and heterologous BNT162b2 vaccinations in individuals 5-40 years of age.

INTRODUCTION: Due to the data scarcity in low- and middle-income countries, we aimed to examine the incidence rate of myocarditis and pericarditis within 30 days after each dose of homologous (3 × BNT162b2) and heterologous prime-boost (2 × BBIBP-CorV/BNT162b2) vaccine regimen among individuals younger than 40 years. METHODS: We conducted a historical control cohort using routinely recorded data from Thai national vaccine and insurance claims databases. Sex-specific incidence rate ratios (IRRs) for myocarditis and pericarditis were calculated for each vaccination strategy and contrasted with incidence rates among the non-immunised population in the pre-COVID-19 period. From August 2021 to September 2022, we tracked the incidence of myocarditis and pericarditis within 30 days after vaccinations using < 40-year-old national population databases. Our reference was the average monthly incidence of these conditions in the non-immunised population from August to October 2019. The exposure of interest was immunisation against the SARS-CoV-2 virus, incorporating the following vaccination strategies: three-dose 3 × BNT162b2 regimen, three-dose 2 × BBIBP-CorV/BNT162b2 regimen, and non-immunisation. RESULTS: For myocarditis, a total of 215 cases were identified among 7,594,965 individuals in the 3 × BNT162b2 cohort, 5 cases among 2,914,643 individuals in the 2 × BBIBP-CorV/BNT162b2 cohort, and 115 cases among 32,424,780 non-immunised individuals. The sex-specific IRRs (95 % confidence intervals) of myocarditis and pericarditis after the homologous vaccination were 3.09 (1.61, 5.93) and 1.84 (0.72, 4.73) for females and 7.43 (3.11, 17.73) and 10.48 (3.90, 28.15) for males, respectively. Conversely, the IRRs of myocarditis after the heterologous vaccination were not significant (females: 2.24 (0.70, 7.17); males: 1.99 (0.48, 8.21)). IRRs could not be obtained for pericarditis after the heterologous vaccination because of the small number of observed events. CONCLUSIONS: The study observed a significantly increased risk of myocarditis and pericarditis following homologous 3 × BNT162b2 vaccination but had insufficient power to confirm an increased risk for myocarditis following the heterologous prime-boost 2 × BBIBP-CorV/BNT162b2 vaccination. The incidence of pericarditis following the heterologous vaccination was too rare to evaluate.

Cross-Risk Between Tuberculosis and COVID-19 in East Java Province, Indonesia: An Analysis of Tuberculosis and COVID-19 Surveillance Registry Period 2020-2022.

INTRODUCTION: Tuberculosis (TB) and COVID-19 are highly transmissible diseases and pose a serious risk to public health. Unfortunately, information on cross-risk between the two diseases was still sparse. Our main objective was to estimate the excess risk among TB patients in getting COVID-19 infection and vice versa. METHODS: The study design was a series of analyses of existing data from TB and COVID-19 registries in East Java Province, Indonesia. The study period was from January 2020 to June 2022. Case-by-case data for this study were obtained from the registration systems for TB and COVID-19 in separate databases. In comparing risk across different groups, adjusting for differences in risk factors that influence the outcome was essential. We overcame this problem by employing a standardized morbidity ratio. RESULTS: Among 92,424 newly diagnosed TB patients, 1,326 were subsequently infected with COVID-19 during the study period, compared with 1,679 expected. The standardized morbidity ratio (95% confidence interval) was 72.61% (60.19%, 85.03%). Among 635,946 newly diagnosed COVID-19-infected patients, 987 subsequently got active TB during the study period against 1,679 expected. The standardized morbidity ratio (95% confidence interval) was 55.33% (49.24%, 61.42%). CONCLUSION: There was no evidence of excess risk in either direction, the excess risk among TB patients in getting COVID-19 infection and vice versa.

Enhancing Learning About Epidemiological Data Analysis Using R for Graduate Students in Medical Fields With Jupyter Notebook: Classroom Action Research.

BACKGROUND: Graduate students in medical fields must learn about epidemiology and data analysis to conduct their research. R is a software environment used to develop and run packages for statistical analysis; it can be challenging for students to learn because of compatibility with their computers and problems with package installations. Jupyter Notebook was used to run R, which enhanced the graduate students' ability to learn epidemiological data analysis by providing an interactive and collaborative environment that allows for more efficient and effective learning. OBJECTIVE: This study collected class reflections from students and their lecturer in the class "Longitudinal Data Analysis Using R," identified problems that occurred, and illustrated how Jupyter Notebook can solve those problems. METHODS: The researcher analyzed issues encountered in the previous class and devised solutions using Jupyter Notebook. These solutions were then implemented and applied to a new group of students. Reflections from the students were regularly collected and documented in an electronic form. The comments were then thematically analyzed and compared to those of the prior cohort. RESULTS: Improvements that were identified included the ease of using Jupyter R for data analysis without needing to install packages, increased student questioning due to curiosity, and students having the ability to immediately use all code functions. After using Jupyter Notebook, the lecturer could stimulate interest more effectively and challenge students. Furthermore, they highlighted that students responded to questions. The student feedback shows that learning R with Jupyter Notebook was effective in stimulating their interest. Based on the feedback received, it can be inferred that using Jupyter Notebook to learn R is an effective approach for equipping students with an all-encompassing comprehension of longitudinal data analysis. CONCLUSIONS: The use of Jupyter Notebook can improve graduate students' learning experience for epidemiological data analysis by providing an interactive and collaborative environment that is not affected by compatibility issues with different operating systems and computers.

COVID-19 pneumonia and the subsequent risk of getting active pulmonary tuberculosis: a population-based dynamic cohort study using national insurance claims databases.

Background: A three-fold increase in the incidence of detecting pulmonary tuberculosis (PTB) in patients hospitalised with COVID-19 pneumonia compared with that in the general population was recently reported; however, this finding may be due to admission bias in the diagnostic investigation. The current cohort study aimed to estimate the risk of having detectable active PTB after SARS-CoV-2 infection. Methods: Insurance claims data in lower Southern Thailand from the 12th regional National Health Security Office, Thailand, were used. Inpatient and outpatient electronic medical records were linked using encrypted identification numbers. Records of individuals aged ≥18 years from 1 April to 30 September 2021 were retrieved to form a dynamic cohort. Exposure status was based on SARS-CoV-2 investigation and pneumonia status: population control (general population who had never been tested), negative reverse transcription-polymerase chain reaction (RT-PCR) control, asymptomatic COVID-19, symptomatic COVID-19 without pneumonia, and COVID-19 pneumonia groups. They were tracked in the databases for subsequent bacteriologically confirmed PTB until 31 March 2022. Findings: Overall, 4,241,201 individuals were recruited in the dynamic cohort and contributed 3,108,224, 227,918, 34,251, 10,325, and 14,160 person-years in the above exposure groups, respectively. Time-varying Cox's regression was conducted using population control as reference. Hazard ratios (95% CIs) of the negative control, asymptomatic, symptomatic COVID-19 without pneumonia, and pneumonia groups were 1.58 (1.08, 2.32), 1.00 (0.25, 4.01), 2.98 (0.74, 11.98), 9.87 (5.64, 17.30) in the first 30 days and 0.97 (0.81, 1.15), 1.41 (0.92, 2.17), 3.85 (2.42, 6.13), and 7.15 (5.54, 9.22) thereafter, respectively. Interpretation: Having had COVID-19 pneumonia, as opposed to the general population status, was strongly associated with a higher hazard of detectable active PTB. In tuberculosis endemic areas, patients with COVID-19 pneumonia should be closely followed up to reduce PTB-related burden. Funding: The Fogarty International Center and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health supported the article processing charges under Award Number D43TW009522.

Tuberculosis Treatment Compliance Under Smartphone-Based Video-Observed Therapy Versus Community-Based Directly Observed Therapy: Protocol for a Cluster Randomized Controlled Trial.

BACKGROUND: The health care system in Thailand has struggled to cope with the COVID-19 pandemic, resulting in decreased administration of community-based directly observed therapy (DOT) for tuberculosis (TB). As an alternative to failed DOT, video-observed therapy (VOT) or the Thai asynchronous VOT system, "TH VOT," was devised. We developed a protocol for a study to test the superiority of VOT over DOT in ensuring treatment compliance. OBJECTIVE: We aim to compare the mean cumulative compliance days of TB patients and their observers under the VOT program with that of individuals under the DOT program during the intensive phase of TB treatment. METHODS: A cluster randomized controlled trial of pulmonary TB patients and their observers will be conducted over a 2-month period. This study will be conducted in the Hat Yai and Meuang Songkhla districts of Songkhla Province, Southern Thailand. A total of 38 observers working at 38 primary care units (PCUs) will be randomized equally into VOT and DOT groups. The TH VOT system will be implemented in 19 PCUs in the VOT group while the other 19 PCUs will continue with the traditional DOT program. Approximately 1-5 TB patients will be under observation, depending on the PCU jurisdiction in which the patients reside. The inclusion criteria for TB patients will be as follows: patients diagnosed with newly active pulmonary TB with a positive acid-fast bacilli sputum smear, aged >18 years, own a smartphone, and are able to use the LINE (Line Corporation) app. The exclusion criteria will be patients with a condition that requires the intervention of a specialist, rifampicin resistance according to a cartridge-based nucleic acid amplification test (GeneXpert MTB/RIF), unable to continue the treatment, and/or alcohol dependence. After the 2-month observation period, all sessions and follow-up clinical outcomes recorded will be retrieved. An intention-to-treat analysis will be performed to assess the compliance of both patients undergoing drug administration and their observers. RESULTS: The Human Research Ethics Committee, Faculty of Medicine, Prince of Songkla University approved the trial on February 19, 2021 (approval number 64-03618-9). The trial was funded in May 2021. The recruitment period will be from January 2022 to July 2022. The observation is scheduled to end by September 2022. CONCLUSIONS: If the VOT shows superiority in observational compliance among patients and observers, the existing DOT policy will be replaced with VOT. TRIAL REGISTRATION: Thai Clinical Trials Registry TCTR20210624002; https://www.thaiclinicaltrials.org/show/TCTR20210624002. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38796.

Video-Observed Therapy With a Notification System for Improving the Monitoring of Tuberculosis Treatment in Thailand: Usability Study.

BACKGROUND: In Thailand, the health care system has struggled to cope with COVID-19, resulting in directly observed therapy for tuberculosis being de-emphasized. A video-observed therapy (VOT) system, or more specifically, the Thai VOT (TH VOT) system, was developed to replace directly observed therapy. According to the pilot study, the system needed notifications to improve usability and user compliance. The updated version of the TH VOT system thus enabled LINE (Line Corporation) notifications. OBJECTIVE: This study aimed to reassess users' compliance with and the usability of the updated TH VOT system. METHODS: This study was conducted in the Hat Yai and Mueang Songkhla districts in Songkhla Province, Southern Thailand, from September 18 to December 1, 2021. The system was used by not only patients with tuberculosis but also tuberculosis staff, who acted as observers in primary health care settings. Some of the observers used the simulated VOT system instead of the actual system due to the lack of participating patients in their jurisdiction. After 30 days of using the system, VOT session records were analyzed to determine the compliance of the patients and observers. The User Experience Questionnaire was administered to reassess the usability of the system and compare the ratings of the participants with the general benchmark scores of the User Experience Questionnaire. The results were summarized to reveal the degree of user compliance and usability in the following three groups: the patients, actual VOT observers, and simulated VOT observers. RESULTS: Of the 19 observers, 10 used the actual VOT system, and the remaining 9 used the simulated VOT system; there were also 10 patients with tuberculosis. The patients, actual VOT observers, and simulated VOT observers exhibited about 70%, 65%, and 50% compliance, respectively, in terms of following the standard operating procedures every day. The scores of all groups on all dimensions were well above the average scores. There was no significant difference in any of the dimensional scores among the three groups. CONCLUSIONS: The updated version of the TH VOT system was deemed usable by both the patients and the health care staff. Compliance with the use of the system was high among the patients but moderate among the observers.

Data Mining for ICD-10 Admission Diagnoses Preceding Tuberculosis within 1 Year among Non-HIV and Non-Diabetes Patients.

Delayed diagnosis of tuberculosis (TB) increases mortality and extends the duration of disease transmission. This study aimed to identify significant ICD-10 admission diagnoses preceding TB. All hospital electronic medical records from fiscal year 2015 to 2020 in the Songkhla Province, Thailand were retrieved. After excluding diabetes and HIV patients, a case-control analysis was performed. Exposures of interest were ICD-10 diagnoses on admissions 1-12 months prior to the visit during which TB was detected. Incident cases of respiratory tuberculosis (A15.0-A16.9) that had been admitted with at least one such exposure were chosen. For every case, controls were retrieved from weekly concurrent OPD patients who had the same 10-year interval of age, sex, and preceding admission and discharge week as the case. The 10 most common comorbidities during hospitalization preceding TB with their relative odds ratios (RORs) and 95% confidence intervals were identified. These included five significant exposures related to lower respiratory infection without adequate TB investigation. Significant RORs ranged from 3.10 (unspecified pneumonia) to 34.69 (hemoptysis). Full TB investigation was not performed due to problems with health insurance. In conclusion, the physicians should be informed about this pitfall, and the insurance system should be revised accordingly.

Development of a Video-Observed Therapy System to Improve Monitoring of Tuberculosis Treatment in Thailand: Mixed-Methods Study.

BACKGROUND: Directly observed therapy programs for monitoring tuberculosis (TB) treatment in Thailand are unsustainable, especially during the COVID-19 pandemic. The current video-observed therapy (VOT) system, the Thai VOT (TH VOT), was developed to replace the directly observed therapy program. OBJECTIVE: This study aimed to describe the VOT system design and identify the potential for system improvements. METHODS: This pilot study was conducted in Na Yong district, a small district in Trang province, south of Thailand. The TH VOT system consists of a smartphone app for patients, a secured web-based platform for staff, items used, and standard operating procedures. There were three groups of users: observers who were TB staff, healthy volunteers as simulated patients, and patients with active TB. All participants were trained to follow the standard operating procedures. After 2-week usage, VOT session records were analyzed to measure the compliance of the patients and observers. The User Experience Questionnaire was used to lead the participant users to focus on 6 standard dimensions of usability, and was supplemented with an in-depth interview to identify potential system improvements from users' experience. RESULTS: Only 2 of 16 patients with currently active TB had a usable smartphone. Sixty of 70 drug-taking sessions among 2 patients and 3 simulated patients in 2 weeks were recorded and uploaded. Only 37 sessions were inspected by the observers within 24 hours. All participants needed a proper notification system. An audit system was also requested. CONCLUSIONS: Before upscaling, the cost of smartphone lending, audit management, and notification systems should be elucidated.