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Alu elements are retrotransposons related to epigenetic modifications. To date, the role of epigenetics in hypertrophic scars from burn remains unknown. Here, our aim was to examine the pathophysiology of hypertrophic scars from an epigenetic perspective. For that, we performed a cross-sectional analytical study using tissue and blood samples from burned and healthy patients (n = 23 each) to detect Alu methylation levels and patterns. The results of the combined bisulfite restriction analysis technique were categorized into four groups based on the methylation status at the CpG dinucleotides from the 5' to the 3' ends of the Alu sequence: hypermethylated (mCmC), hypomethylated (uCuC), and partially methylated (uCmC and mCuC). Alu methylation levels were significantly lower in hypertrophic scar tissues than in normal skin (29.37 ± 2.49% vs. 35.56 ± 3.18%, p = 0.0002). In contrast, the levels were significantly higher in white blood cells from blood samples of burned patients than in those of control blood samples (26.92 ± 4.04% vs. 24.58 ± 3.34%, p = 0.0278). Alu total methylation (mC) and the uCmC pattern were significantly lower, whereas uCuC was significantly higher, in hypertrophic scar tissues than in normal skin (p < 0.0001). Receiver operating characteristic analysis indicated that the uCmC and uCuC patterns are useful as hypertrophic scar DNA methylation markers after burn, with 91.30% sensitivity and 96.23% specificity and 100% sensitivity and 94.23% specificity, respectively. Our findings suggest that epigenetic modifications play a major role in hypertrophic scar pathogenesis, and may be the starting point for developing a novel technique for burn scar treatment.

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.

Both a leaky gut (a barrier defect of the intestinal surface) and gut dysbiosis (a change in the intestinal microbial population) are intrinsic to sepsis. While sepsis itself can cause dysbiosis, dysbiosis can worsen sepsis. The leaky gut syndrome refers to a status with which there is an increased intestinal permeability allowing the translocation of microbial molecules from the gut into the blood circulation. It is not just a symptom of gastrointestinal involvement, but also an underlying cause that develops independently, and its presence could be recognized by the detection, in blood, of lipopolysaccharides and (1→3)-β-D-glucan (major components of gut microbiota). Gut-dysbiosis is the consequence of a reduction in some bacterial species in the gut microbiome, as a consequence of intestinal mucosal immunity defect, caused by intestinal hypoperfusion, immune cell apoptosis, and a variety of enteric neuro-humoral-immunity responses. A reduction in bacteria that produce short-chain fatty acids could change the intestinal barriers, leading to the translocation of pathogen molecules, into the circulation where it causes systemic inflammation. Even gut fungi might be increased in human patients with sepsis, even though this has not been consistently observed in murine models of sepsis, probably because of the longer duration of sepsis and also antibiotic use in patients. The gut virobiome that partly consists of bacteriophages is also detectable in gut contents that might be different between sepsis and normal hosts. These alterations of gut dysbiosis altogether could be an interesting target for sepsis adjuvant therapies, e.g., by faecal transplantation or probiotic therapy. Here, current information on leaky gut and gut dysbiosis along with the potential biomarkers, new treatment strategies, and future research topics are mentioned.

This study aimed to determine the real-world effectiveness of bi- or quadrivalent human papillomavirus (HPV) vaccines in Thai adult women ≥5 years post-vaccination in reducing HPV 16/18-associated low-grade squamous intraepithelial lesions or worse (LSIL+), atypical squamous cells of undetermined significance or worse (ASC-US+), and HPV 16/18 positivity.A retrospective cohort study was conducted among Thai women aged 20-45 years in Bangkok. The vaccinated and unvaccinated groups were matched according to baseline years. HPV/Pap test results were collected from the medical records and/or obtained by cervical sample collection at the study sites. Adjusted hazard ratios were measured using multivariable Cox regression analyses.A total of 993 participants (493 vaccinated and 500 unvaccinated) were enrolled from 2018 to 2019. The median ages at baseline of the vaccinated and unvaccinated groups were 33 years (interquartile range [IQR] 27-38) and 34 years (IQR 30-38), respectively. The median follow-up periods were 7.3 years (IQR 6.1-8.6) and 7.2 years (IQR 5.8-8.9) for the vaccinated group and the unvaccinated group, respectively. More women in the vaccinated group were single (29.2% vs. 13.2%, P 0.001) and university graduates (83.2% vs. 75.4%, P = 0.009). The vaccinated and unvaccinated groups had similar personal monthly incomes (20,000 THB/month, 63.9% vs. 62.4%, respectively, P = 0.685). There were no cases of HPV 16/18-associated LSIL+ in the vaccinated group, whereas there were four cases in the unvaccinated group. HPV vaccine effectiveness was 88.0% (95% CI 2.0-98.5) in the reduction of HPV 16/18-associated ASC-US+, and 84.6% (95% CI 43.5-95.8) in the reduction of HPV 16/18 positivity.HPV vaccine effectiveness was high in adult women in a real-world scenario in a developing country. Free HPV vaccination in adult women in this age group should be further explored when vaccine supplies are not limited. (HPV: human papillomavirus. LSIL+: low-grade squamous intraepithelial lesion or worse. ASC-US+: atypical squamous cells of undetermined significance or worse).

To describe the clinical characteristics of varicella patients seeking medical consultation and the use of antimicrobials for their management in Thailand in the absence of universal varicella vaccination (UVV). A multicenter, retrospective chart review of 260 children and adults with a primary diagnosis of varicella was conducted at one private and three public hospitals in Bangkok, Thailand. Charts of varicella patients (inpatient or outpatient) were randomly selected over a 5-year period. Key outcomes included clinical complications and the use of antibiotics, antivirals, and other medications. Charts of 200 children (mean age 5.7 years, range 0.3–16 years) and 60 adults (mean age 27.9 years, range 18–50 years) were reviewed. Fourteen patients (including 8 children) were hospitalized. Five percent of the children and none of the adults were immunocompromised. At least 1 varicella-related complication was reported by 7.3% (7% of children, 8.3% of adults, p = .778) of all patients, including 57.1% (62.5% of children, 50% of adults) of inpatients (p < .001, compared with outpatients). Skin/soft tissue infection (47.7%) and dehydration (47.4%) were the most common complications. Antivirals (mainly oral acyclovir) were prescribed to 46.5% of patients (31.5% of children, 96.7% of adults, p < .001). Antibiotics were prescribed to 20.8% of patients (19% of children, 26.7% of adults, p = .199). Topical, oral, and intravenous antibiotics were prescribed to 12.3%, 8.5%, and 1.2% of patients, respectively. Antimicrobial prescriptions were higher among adults (p < .001) and immunocompromised patients (p = .025). Apart from antimicrobials, acetaminophen (62.3%) and oral antihistamines (51.5%) were the most prescribed. A considerable number of varicella patients, both children and adults, seeking medical consultation in Thai hospitals are prescribed antibiotics and antivirals, with one-fifth of patients being prescribed an antibiotic and almost half prescribed an antiviral. The study may be of interest to policymakers in Thailand and other Asia-Pacific countries considering UVV implementation.

Pneumonia is a leading cause of hospitalization and death among elderly adults. We performed a retrospective and prospective observational study to describe the etiology, clinical course, and outcomes of pneumonia for patients 60 years and older in Thailand. We enrolled 490 patients; 440 patients were included in the retrospective study and 50 patients were included in the prospective study. The CURB-65 score and a modified SMART-COP score (SMART-CO score) were used to assess disease severity. The median patient age was 80 years (interquartile range, 70–87 years); 51.2% were men. Klebsiella pneumoniae (20.4%) and Pseudomonas aeruginosa (15.5%) were the most common causative agents of pneumonia. A significant minority (23%) of patients were admitted to the intensive care unit (ICU), and mortality among this subset of patients was 45%. Most patients (80.8%) survived and were discharged from the hospital. The median duration of hospitalization was 8 days (interquartile range, 4–16 days). In contrast, 17.6% of patients died while undergoing care and 30-day mortality was 14%. Factors significantly associated with mortality were advanced age (P = 0.004), male sex (P = 0.005), multiple bacterial infections (P = 0.007; relative risk [RR], 1.88; 95% confidence interval [CI], 1.19–2.79), infection with multi-drug-resistant/extended-spectrum B-lactamase-producing organisms (P < 0.001; RR, 2.82; 95% CI, 1.83–4.85), ICU admission (P < 0.001; RR, 1.8; 95% CI, 1.4–2.3), and complications of pneumonia (P < 0.001; RR, 2.5; 95% CI, 1.8–3.4). Patients with higher SMART-CO and CURB-65 scores had higher rates of ICU admission and higher 30-day mortality rates (P < 0.001). These results emphasize the importance of Gram-negative bacteria, particularly K. pneumoniae and P. aeruginosa, as major causes of pneumonia among the elderly in contrast to other reports, Streptococcus pneumoniae is a common cause of pneumonia among elderly individuals worldwide. The SMART-COP and CURB-65 scores were developed to assess pneumonia severity and predict mortality of young adults with pneumonia. Few studies have examined the appropriateness of these scores for elderly patients with multiple comorbidities. A limited number of studies have used modified versions of these scores among elderly individuals. We found that Gram-negative bacteria has a major role in the etiology of pneumonia among elderly individuals in Southeast Asia. A significant proportion of elderly individuals with low CURB-65 scores were admitted to the hospital, indicating that hospital admission may reflect fragility among elderly individuals with low CURB-65 scores. The modified SMART-COP score (SMART-CO score) sufficiently predicted intensive care unit admission and the need for intensive vasopressor or respiratory support. A SMART-CO score ≥ 7 accurately predicted 30-day mortality.

The hallmark of severe dengue infection is the increased vascular permeability and hemodynamic alteration that might be associated with an intestinal permeability defect. However, the mechanisms underlying the gastrointestinal-related symptoms of dengue are not well characterized. A prospective observational study was conducted on patients with dengue who were categorized according to: (i) febrile versus critical phase and (ii) hospitalized patients with versus without the warning signs to evaluate the gut barrier using lactulose-to-mannitol excretion ratio (LEMR). Serum endotoxins, (1→3)-β-D-glucan (BG), and inflammatory parameters were measured. A total of 48 and 38 patients were enrolled in febrile illness and critical phase, respectively, while 22 and 64 patients presented with or without the warning signs, respectively. At enrollment, a positive LEMR test was found in 20 patients (91%) with warning signs, regardless of phase of infection. Likewise, serum endotoxins and BG, the indirect biomarkers for leaky gut, prominently increased in patients who developed severe dengue when compared with the non-severe dengue (endotoxins, 399.1 versus 143.4 pg/mL (p &lt, 0.0001), BG, 123 versus 73.8 pg/mL (p = 0.016)). Modest impaired intestinal permeability occurred in dengue patients, particularly those with warning signs, and were associated with endotoxemia and elevated BG. Thus, leaky gut syndrome might be associated with severity of dengue infection.

SummaryBackgroundProduction of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based Newcastle disease virus vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It’s being developed in Thailand, Vietnam, and Brazil; herein are initial results from Thailand.MethodsThis phase 1 stage of a randomised, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Mahidol University (Bangkok). Healthy adults aged 18-59 years, non-pregnant and negative for SARS-CoV-2 antibodies were eligible. Participants were block randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 µg±CpG1018 (a toll-like receptor 9 agonist), 3 µg±CpG1018, 10 µg, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited and spontaneously reported adverse events (AEs) during 7 and 28 days after each vaccination, respectively. Secondary outcomes were immunogenicity measures (anti-S IgG and pseudotyped virus neutralisation). An interim analysis assessed safety at day 57 in treatment-exposed individuals and immunogenicity through day 43 per protocol. ClinicalTrials.gov (NCT04764422).FindingsBetween March 20 and April 23, 2021, 377 individuals were screened and 210 were enrolled (35 per group); all received dose one; five missed dose two. The most common solicited AEs among vaccinees, all predominantly mild, were injection site pain (InterpretationNDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 µg and 3 µg+CpG1018 formulations advanced to phase 2.FundingNational Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA)

BACKGROUND: Two main strategies to cope with the coronavirus disease 2019 (COVID-19) pandemic-lockdown (social restriction) and non-lockdown (herd immunity plan)-have been implemented in several countries. OBJECTIVE: This study aims to statistically compare the outcomes of the two strategies, represented by data from Thailand and Sweden, respectively. METHODS: Data for COVID-19 pandemic control from Thailand, representing social restriction, versus data from Sweden, representing the herd immunity plan, collected from January 13 to May 31, 2020, were analyzed by using the SIR (susceptible, infectious, recovered) model. RESULTS: The SIR model analysis demonstrated a beneficial effect of each model on the attenuation of the mortality rate, with lower mortality in social restriction and shorter overall pandemic duration in the herd immunity plan. However, the herd immunity plan demonstrated a higher mortality rate than social restriction (46.9% versus 1.9%) despite the later entry of the virus in Sweden. When the SIR model was used for predicting the COVID-19 status, Sweden was shown to likely end its COVID-19 epidemic earlier than Thailand (268 vs. 368 days). With the nonlinear estimation, at least one log difference between total confirmed cases versus active cases could be used as an indicator for relaxation of the lockdown policy in Thailand. CONCLUSIONS: Both the social restriction and herd immunity plans are beneficial for COVID-19 pandemic control in terms of the amelioration of pandemic mortality. The cumulative number of total recovered cases might be a potential parameter that could be used for determining the policy direction for COVID-19 control.

Background Together with clinical correlation, nontreponemal titers are used to monitor treatment outcomes. Syphilis patients with HIV and without HIV coinfection were found to have different serological responses after treatment. This study aims to determine time to serological cure for treatment of syphilis and factors associated with it in patients with and without HIV. Method A descriptive study of syphilis patients who visited Bangrak STIs Center between January 1, 2007, and December 31, 2016. Univariate analysis was done to determine factors associated with serological outcomes. Survival curve analysis and multivariate Cox regression analysis were applied to compare time to serological cure between patients with various characteristics. Results Of 497 syphilis patients, 62.1% had serological cure, 2.2% had nonresponse, 4.6% had treatment failure or reinfection, 9.9% had serofast status, and 21.2% were undetermined because of loss to follow-up. The time to serological cure was 110 days (95% confidence interval [CI], 59-163 days) and 102 days (95% CI, 94-110 days) among patients with HIV and without HIV, respectively (P = 0.162). Time to serological cure was significantly faster in early syphilis and baseline titer ≥1:32. After adjustment with the Cox regression model, patients with early syphilis were associated with serological cure with a hazard ratio of 1.75 (95% CI, 1.32-2.32). Time to serological cure among early syphilis patients was significantly longer in HIV-positive than HIV-negative patients (P = 0.002), whereas no difference was observed in late syphilis (P = 0.104). Conclusion Early syphilis was associated with faster time to serological cure. HIV patients with early syphilis took longer time to reach serological cure than did HIV-negative patients, whereas no such a difference was observed in late syphilis.

Human papillomavirus (HPV) is the most common sexually transmitted infection, with 15 HPV types related to cervical, anal, oropharyngeal, penile, vulvar, and vaginal cancers. However, cervical cancer remains one of the most common cancers in women, especially in developing countries. Three HPV vaccines have been licensed: bivalent (Cervarix, GSK, Rixensart, Belgium), quadrivalent (Merck, Sharp & Dome (Merck & Co, Whitehouse Station, NJ, USA)), and nonavalent (Merck, Sharp & Dome (Merck & Co, Whitehouse Station, NJ, USA)). The current HPV vaccine recommendations apply to 9 years old and above through the age of 26 years and adults aged 27–45 years who might be at risk of new HPV infection and benefit from vaccination. The primary target population for HPV vaccination recommended by the WHO is girls aged 9–14 years, prior to their becoming sexually active, to undergo a two-dose schedule and girls ≥ 15 years of age, to undergo a three-dose schedule. Safety data for HPV vaccines have indicated that they are safe. The most common adverse side-effect was local symptoms. HPV vaccines are highly immunogenic. The efficacy and effectiveness of vaccines has been remarkably high among young women who were HPV seronegative before vaccination. Vaccine efficacy was lower among women regardless of HPV DNA when vaccinated and among adult women. Comparisons of the efficacy of bivalent, quadrivalent, and nonavalent vaccines against HPV 16/18 showed that they are similar. However, the nonavalent vaccine can provide additional protection against HPV 31/33/45/52/58. In a real-world setting, the notable decrease of HPV 6/11/16/18 among vaccinated women compared with unvaccinated women shows the vaccine to be highly effective. Moreover, the direct effect of the nonavalent vaccine with the cross-protection of bivalent and quadrivalent vaccines results in the reduction of HPV 6/11/16/18/31/33/45/52/58. HPV vaccination has been shown to provide herd protection as well. Two-dose HPV vaccine schedules showed no difference in seroconversion from three-dose schedules. However, the use of a single-dose HPV vaccination schedule remains controversial. For males, the quadrivalent HPV vaccine possibly reduces the incidence of external genital lesions and persistent infection with HPV 6/11/16/18. Evidence regarding the efficacy and risk of HPV vaccination and HIV infection remains limited. HPV vaccination has been shown to be highly effective against oral HPV type 16/18 infection, with a significant percentage of participants developing IgG antibodies in the oral fluid post vaccination. However, the vaccines’ effectiveness in reducing the incidence of and mortality rates from HPV-related head and neck cancers should be observed in the long term. In anal infections and anal intraepithelial neoplasia, the vaccines demonstrate high efficacy. While HPV vaccines are very effective, screening for related cancers, as per guidelines, is still recommended.