Department of Disease Control

Immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic strategy for canine oral malignant melanoma (OMM). However, only a subset of cases have shown clinical responses. Additionally, predictive biomarkers for the efficacy of ICIs in veterinary medicine are yet to be established. Tumour-infiltrating lymphocytes (TILs) are predictive biomarkers for ICI therapy in humans. In this study, we aimed to investigate the predictive utility of TILs for canine OMM treated with ICI therapy. Immunohistochemistry was performed on pre-treatment pathological tissues to detect cells positive for CD3 (pan-T cell marker), Granzyme B (cytotoxic T lymphocyte or natural killer cell marker) and Foxp3 (regulatory T cell marker). Further, we analysed the infiltration patterns of these cells and their prognostic utility for anti-programmed cell death ligand 1 (PD-L1) antibody therapy. There were variances in the infiltration levels of each TIL subset; further, we observed several TIL infiltration patterns in canine OMM. Survival analysis revealed that high infiltration of CD3+ and Granzyme B+ cells was significantly associated with prolonged progression-free survival and overall survival. Furthermore, the immune cell composition ratio, which reflected the balance between cytotoxic and regulatory cells, was significantly associated with survival time. These findings suggest that canine OMM exhibits immunological phenotypes analogous to those observed in human cancers. Taken together, the TIL profile holds significant potential as a prognostic biomarker for canine OMM treated with anti-PD-L1 antibody therapy.

To assess the impact of an integrated model of care in curing hepatitis C in people who use drugs in Thailand. The C-Free Study enrolled people with current or prior drug use and their partners in a prospective cohort at community drop-in centres providing harm reduction services. Participants were screened for human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV) and sexually transmitted infections. Eligible participants with HCV infection received a 12-week course of sofosbuvir-velpatasvir. The main impact outcome was sustained virological response, measured 12 weeks after treatment completion. Between June 2019 and April 2023, we enrolled 2871 participants in 10 sites across Thailand: 1601 (55.8%) had HCV antibodies; 1275 (44.4%) had active HCV infection; 846 (29.5%) had HIV; and 221 (7.7%) had HBV. Of 1134 participants with active HCV who started treatment with sofosbuvir-velpatasvir, 939 (82.8%) achieved a sustained virological response. Among 987 participants completing treatment, 95.1% achieved a sustained virological response. In multivariable analysis, age > 40 years (adjusted odds ratio, aOR: 1.63; 95% confidence interval, CI: 1.04-2.54) and poor treatment adherence (aOR: 0.06; 95% CI: 0.02-0.20) were associated with sustained virological response. Of 34 serious adverse events during treatment, six led to treatment discontinuation including five non-treatment-related deaths. Community-based HCV treatment of people who use drugs in Thailand, within harm reduction settings, is safe and effective. Integration of this strategy into national programmes could enhance HCV elimination in people who use drugs.

The control of ticks is challenging owing to their ubiquity, complex ecologies, and difficulties relating to costs and non-target impacts of chemical control programs. Nature-based solutions centre around co-opting natural processes and biodiversity to address socio-environmental problems; and in some cases, rewilded species can provide nature-based solutions. In northern Japan, the winter ecology of ticks is poorly studied, though some species are believed to overwinter under the snow. Winter grazing activity of rewilded horses may disturb overwintering ticks, exposing them to sub-zero temperatures and killing them, thereby providing a nature-based solution to tick control. In this study we sought to ascertain: (i) whether ticks in Japan overwinter in leaflitter under the snow, (ii) whether the winter grazing activity of semi-rewilded horses is associated with reduced springtime tick abundance, (iii) whether semi-rewilded horses serve as key hosts for ticks during springtime. Paired leaflitter sampling undertaken at 10 sites during autumn and winter, respectively, showed that Haemaphysalis ticks overwinter in leaflitter under the snow. Using six paired 25 m2 exclusion-grazing plots we tested whether winter horse grazing was associated with reduced springtime tick abundances but found no significant relationships. Springtime surveys revealed extremely low tick loads (0.2 ticks per horse) and prevalences (12%) on semi-rewilded horses. This suggests that while the winter grazing activities of horses may not appreciably reduce tick abundances, that horses likely do not serve as important amplifying hosts of ticks in northern Japan and that rewilded horses are neither a help nor hinderance to local tick control efforts in this region.

BackgroundFollowing border closures implemented during the COVID-19 pandemic, Thailand subsequently reopened its international borders, employing public health policy for international travelers (PHPIT) to mitigate the importation of COVID-19 cases and minimize potential missed cases. These measures included departure country risk classification, vaccination certificate requirement, pre-departure and entry testing, and quarantine.MethodsTo assess the effectiveness of these interventions, we developed a cross-border control model, which integrates cluster analysis and mathematical modeling to estimate reductions in missed cases in Thailand under various scenarios.ResultsOur findings indicated that, as a single measure, when compared with implementing no interventions, quarantine for 1, 3, 5, 7, 10, and 14 days reduced missed cases by 45%, 58%, 72%, 80%, 88%, and 94%, respectively. Departure country risk classification reduced missed cases by up to 72% and vaccination certificate requirement by up to 24%. Testing once at 72, 48, 24, or 0 h pre-departure reduced missed cases by 5%, 7%, 10%, and 14% respectively. Entry testing (the “test-and-go” policy) reduced missed cases by 29%. Strategically combining quarantine with other PHPIT measures could achieve a 46–98% reduction in missed cases, with the maximum reduction in missed cases when implementing 14-day quarantine together with pre-departure testing.ConclusionsQuarantine could serve as a standard measure to minimize missed cases and be optimized by a vaccination certificate requirement. Meanwhile, testing and departure country risk classification could be withdrawn due to their minimal effectiveness and potential for discrimination, respectively. The combinations and their optimization should be guided by domestic transmission dynamics, healthcare system capacities, societal perspectives, and economic adaptability. Future PHPIT implementation should incorporate pre-evaluation to balance intervention effectiveness, equity for international travelers, and public health and economic security.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12889-025-25811-5.

The oral mucosa is a key barrier and entry point for microorganisms into the gastrointestinal tract. Interleukin-17 (IL-17) and T helper 17 (Th17) cells contribute to mucosal defense against bacterial and fungal pathogens. Gingival fibroblasts recruit neutrophils, construct a mechanical barrier of gingival tissue, and produce osteoprotegerin, which prevents bone resorption. In periodontitis, inflammatory cytokines induce RANKL expression by osteoblasts and periodontal ligament fibroblasts, resulting in alveolar bone resorption. In diabetes mellitus, excessive IL-17 activity increases the risk of periodontal tissue destruction and fungal infections. In patients with diabetes, periodontitis worsens insulin resistance and glycemic control while introducing periodontopathic bacteria and Th17 cells to the gut, exacerbating intestinal inflammation. Infection with periodontopathic bacteria sharing homology with β2 glycoprotein I (β2GPI) may induce antibodies against β2GPI, increasing blood clot risk. Thus, in patients with diabetes and periodontitis, symptoms vary due to localized and systemic immune responses to bacteria and fungi, necessitating a comprehensive understanding for accurate diagnosis and treatment. The biopsychosocial model aids in addressing these complexities, while the common risk approach and cognitive-behavioral therapy address social and psychological challenges. Therefore, comprehensive treatment strategies are necessary for managing periodontitis in patients with diabetes, considering both microbial factors and immune responses.

Cancer in dogs remains a major challenge in modern veterinary medicine. Immunotherapyusing immune checkpoint inhibitors (ICIs) is available for various human tumor types, andrecent veterinary clinical studies have shown that ICIs are a promising approach fortreating canine cancers. A canine chimeric anti-PD-L1 antibody, c4G12 (HFC-L1), has beeninvestigated for canine cancer immunotherapy; however, its clinical benefits have not beenwell characterized in tumors other than pulmonary metastatic (stage IV) oral malignantmelanoma (OMM). To explore the efficacy and safety of HFC-L1, we conducted a clinicalstudy in dogs with stage I–III OMM or other tumor types (n=12). HFC-L1treatment at a dose of 5 mg/kg every 2 weeks was well tolerated, and no grade 3 or highertreatment-related adverse events were reported. Among the dogs eligible for responseevaluation (n=10), a partial response was observed in one dog withsquamous cell carcinoma, resulting in an objective response rate of 10%. In addition, in adog with ceruminous cell carcinoma, clinical evidence of a tumor response was observed inmetastatic lung lesions. Together, these results suggest that the HFC-L1 therapy isapplicable for the treatment of various tumor types, although its clinical benefits shouldbe further evaluated in clinical studies involving a larger number of dogs with each tumortype.

BackgroundMalaria remains a leading cause of morbidity and mortality in many low- and middle-income countries (LMICs). Factors outside the health sector, including social determinants, such as economic status remain important drivers of malaria in these settings. However, social determinants of malaria generally remain unaddressed in preventing the disease, with the limited existing evidence overly descriptive and fragmented. MethodsA mixed-methods systematic review was conducted to thematically synthesize the current evidence on the social determinants of malaria in LMICs. PubMed, Web of Science, and Scopus were searched to identify English articles on the social determinants of malaria published between January 2013 and December 2023. Search terms such as social determinant, socio-cultural, and socioeconomic factors were used. Articles that did not meaningfully engage with the social determinants were excluded.ResultsThe 39 articles included in the review were mostly cross-sectional and qualitative studies of moderate quality, in general. Findings indicate a range of social determinants of malaria related to the following overarching themes: environmental factors, access to and use of treatment, preventive interventions use, housing, stakeholder influence, livelihoods and economic development, and poverty. The various social determinants influenced malaria in different ways, including limiting access and use of preventive and treatment interventions and increased exposure to mosquitoes. Poverty and gender intersected with other social determinants such as housing and livelihoods.ConclusionDifferent social determinants of malaria are key drivers of malaria in LMICs. The findings emphasize the need for malaria control efforts to consider social determinants at all levels, including funding, implementation, and evaluation.

Parental interaction in learning-promoting activities is crucial for supporting early childhood development. This study aimed to assess the level of parental interaction among children aged 2-4 years in Thailand and to identify determinants associated with parental interaction. A cross-sectional analysis was conducted using data from the 2022 Multiple Indicator Cluster Survey (MICS), which included a nationally representative sample of 7003 parents of children aged 2-4 years. Parental interaction was assessed through six activities promoting early stimulation and responsive care. Interaction levels were categorized as high (participation in four or more activities) or low (fewer than four activities). Multivariable logistic regression was employed to analyze associations between parental interaction levels and household and participant characteristics. The study found that 88.1% of parents reported high levels of interaction with their children. Children outside Bangkok had lower odds of high interaction, particularly in the Central (AOR=0.33), North (AOR=0.31), Northeast (AOR=0.44), and South (AOR=0.38) regions. Higher odds of high interaction were associated with maternal education above secondary level (AOR=2.00), the highest wealth quintile (AOR=2.48), living with either (AOR=2.14) or both parents (AOR=2.59), being in a non-Thai-speaking household (AOR=1.75), and having three or more books at home (AOR=3.63). Nearly 12% of parents reported low levels of interaction with their children aged 2-4 years, with disparities associated with regional and socioeconomic factors. Policy efforts should prioritize integrating parental support into early childhood education programs and enhancing access to resources, such as children's books and community libraries, particularly for socioeconomically disadvantaged groups.

Though Helmholtz resonators now find widespread application within silencers and sensitive acoustic spaces, they bear their name from a scientist who pursued neither of these ends. Rather, Hermann Von Helmholtz employed his namesake resonators as a convienent tool to analyze individual tonal components of complex musical sounds, essentially positioning the human observer as a signal analyzer augmented by a bank of tuned resonators comprising variable filters within the signal chain. In the lead up to the development of the sound level meter, both of these roles were ultimately replaced by electroacoustic technologies. However, this was not immediate, and echoes of Helmholtz’s apparatus were seen in such measurement techniques as Wallace Sabine’s aural determination of reverberation time, the resonant enclosue of the Tucker hot-wire microphone, and binaural methods of sound ranging during World War I. This presentation traces the physical and human antecedents to the modern electronic sound level meter, concluding with a few specialized cases where they can still find use today.