Safety and immunogenicity of locally produced trivalent inactivated influenza vaccine (Tri Fluvac) in healthy Thai adults aged 18-64 years in Nakhon Phanom: A Phase III double blinded, three-arm, randomized, controlled trial.

BACKGROUND: Domestic influenza vaccine production facilitates a sustainable supply for mitigating seasonal influenza and improves national health security by providing infrastructure and experience for pandemic vaccine production, if needed. METHODS: A Phase III, double blind, randomized controlled trial was conducted from Sep 2019-Oct 2020 in healthy adults 18-64 years in Nakhon Phanom, Thailand. Randomization (3:3:1) compared study vaccine (Tri Fluvac), saline placebo, and an active comparator (licensed vaccine). Primary outcomes were superior efficacy compared to placebo based on RT-PCR-confirmed influenza virus infection within 12 months and non-inferiority compared to active comparator based on immunogenicity (HAI assay) at 28 days. Safety was also assessed. RESULTS: The trial enrolled 4,284 participants (Tri Fluvac = 1,836; placebo = 1,836; active comparator = 612). There were 29 RT-PCR positive influenza infections (10 Tri Fluvac, 5.5/1,000 PY; 19 placebo, 10.4/1,000PY; 0 comparator) for an absolute protective efficacy of 46.4 (95 % CI = -22.0-76.5) compared with placebo, but the power was 43.7 %. Seroconversion difference rates between Tri Fluvac and comparator at Day 28 were 1.74 (95 % CI: -2.77, 6.25), 2.22 (-2.40, 6.84), and -0.57 (-5.41, 4.27) for A(H1N1), A(H3N2), and B strains, respectively. Adverse and severe adverse events occurred in 175 (9.5 %) Tri Fluvac, 177 (10.8 %) placebo, and 66 (10.8 %) comparator arms (p-value = 0.437, Tri Fluvac vs. comparator) CONCLUSIONS: Tri Fluvac was well tolerated, and immunogenicity was non-inferior to the active comparator, meeting U.S. Food and Drug Administration (FDA) criteria for adult vaccine licensure. Few acute respiratory infections were reported during intense COVID-19 pandemic restrictions, resulting in insufficient power to evaluate clinical efficacy.

Does prior vaccination affect the immune response to seasonal influenza vaccination among older adults? Findings from a prospective cohort study in a Northeastern Province of Thailand.

BACKGROUND: We measured the immunogenicity of seasonal trivalent inactivated influenza vaccines (IIV3) among older Thai adults and the effect of one-year prior vaccination status on immune responses. METHOD: Adults aged ≥65 years (n = 370) were vaccinated with Southern Hemisphere IIV3 in 2015. Hemagglutination inhibition assays were performed using goose red blood cells on sera collected from the participants at baseline and after 1, 6, and 12 months of vaccination. Prior year vaccination (in 2014) was verified with the national health security office database. We analyzed the associations between prior vaccination and geometric mean titers (GMT) at each time point using generalized linear regression on logged transformed titers, and seroprotection and seroconversion using Log-binomial regression. RESULTS: At baseline, previously vaccinated participants (n = 203) had a significantly higher GMT and seroprotection against all three influenza strains than those previously unvaccinated (n = 167) (all p-values <0.001). Seroprotection rates were similar after one month in both groups for A(H1N1)pdm09 (adjusted risk ratio [aRR] 1.10, 95% CI 0.97-1.25), and A(H3N2) (aRR 1.08, 95% CI 0.87-1.33), but higher in previously vaccinated persons for B (aRR 1.20, 95% CI 1.08-1.32). At 12 months, 50% or more had seroprotection in previously vaccinated group with no difference between previously vaccinated or unvaccinated persons. Seroconversion was lower in the previously vaccinated group for A(H1N1)pdm09 (aRR 0.62, 95% CI 0.43-0.89), but did not differ between the two groups for A(H3N2) (aRR 0.94, 95% CI 0.69-1.28) and B (aRR 0.85, 95% CI 0.60-1.20). CONCLUSION: Influenza vaccination elicited good humoral response in older Thai adults. While seroconversion seemed attenuated in persons previously vaccinated for influenza A(H1N1)pdm09 (the only vaccine strain not to change), this was not apparent for influenza A(H3N2) and B, and prior vaccination was not associated with any inhibition in seroprotection.

Underlying cardiopulmonary conditions as a risk factor for influenza and respiratory syncytial virus infection among community-dwelling adults aged ≥ 65 years in Thailand: Findings from a two-year prospective cohort study.

BACKGROUND: Adults with cardiopulmonary conditions may be at increased risk of influenza and respiratory syncytial virus (RSV) infection, but it is not well-established and few data are available from middle-income countries. METHODS: Using data from a prospective cohort study of influenza vaccine effectiveness, we estimated and compared the incidences of influenza and RSV between community-dwelling Thai adults aged ≥ 65 years with and without cardiopulmonary conditions. During May 2015-May 2017, older adults in a rural province in Thailand were followed-up with weekly surveillance for acute respiratory illness (ARI), defined broadly as new onset or worsening of cough with or without fever, and hospitalized ARI. When ill, nasal self-swabs and/or nasopharyngeal swabs were collected for reverse-transcription polymerase chain reaction testing. We used Poisson regression to calculate incidence rate ratios (IRR), adjusting for age, sex, current smoking, number of hospital visits, weekly influenza activity, and influenza vaccination. RESULTS: Overall, 3220 adults with a median age of 71 years (IQR 68-76) were enrolled; 1324 (41.1%) were male; and 313 (9.7%) had ≥1 underlying cardiopulmonary condition, most commonly chronic obstructive pulmonary disease (131; 41.2%) or asthma (73; 23.3%). Participants with cardiopulmonary conditions had higher incidences of ARI, influenza, and RSV than those without (Adjusted IRR: 1.84, 95% CI 1.64-2.07; 1.86, 95% CI 1.07-3.26; 2.04, 95% CI 1.11-3.76, respectively). CONCLUSION: Older adults in rural Thailand with cardiopulmonary conditions have increased rates of ARI, influenza, and RSV infections. Our findings support efforts to ensure this population has access to influenza vaccines and other respiratory illness prevention measures.

Comparison of DNA extraction kits for detection of Burkholderia pseudomallei in spiked human whole blood using real-time PCR.

Burkholderia pseudomallei, the etiologic agent of melioidosis, is endemic in northern Australia and Southeast Asia and can cause severe septicemia that may lead to death in 20% to 50% of cases. Rapid detection of B. pseudomallei infection is crucial for timely treatment of septic patients. This study evaluated seven commercially available DNA extraction kits to determine the relative recovery of B. pseudomallei DNA from spiked EDTA-containing human whole blood. The evaluation included three manual kits: the QIAamp DNA Mini kit, the QIAamp DNA Blood Mini kit, and the High Pure PCR Template Preparation kit; and four automated systems: the MagNAPure LC using the DNA Isolation Kit I, the MagNAPure Compact using the Nucleic Acid Isolation Kit I, and the QIAcube using the QIAamp DNA Mini kit and the QIAamp DNA Blood Mini kit. Detection of B. pseudomallei DNA extracted by each kit was performed using the B. pseudomallei specific type III secretion real-time PCR (TTS1) assay. Crossing threshold (C T ) values were used to compare the limit of detection and reproducibility of each kit. This study also compared the DNA concentrations and DNA purity yielded for each kit. The following kits consistently yielded DNA that produced a detectable signal from blood spiked with 5.5×10(4) colony forming units per mL: the High Pure PCR Template Preparation, QIAamp DNA Mini, MagNA Pure Compact, and the QIAcube running the QIAamp DNA Mini and QIAamp DNA Blood Mini kits. The High Pure PCR Template Preparation kit yielded the lowest limit of detection with spiked blood, but when this kit was used with blood from patients with confirmed cases of melioidosis, the bacteria was not reliably detected indicating blood may not be an optimal specimen.