In the early stages of human papillomavirus (HPV) infection, the viral proteins elicit specific immune responses that can participate to regression of ano-genital lesions. HPV E6 protein for instance can reduce type I interferon (IFN) including IFN-κ that is involved in immune evasion and HPV persistence. To evaluate the role of E2 protein in innate immunity in HPV16-associated cervical lesions, genome-wide expression profiling of human primary keratinocytes (HPK) transduced by HPV16 E2 was investigated using microarrays and innate immunity associated genes were specifically analyzed. The analyses showed that the expression of 779 genes was modulated by HPV16E2 and 92 of them were genes associated with innate immunity. Notably IFN-κ and STING were suppressed in HPK expressing the E2 proteins of HPV16 or HPV18 and the trans-activation amino-terminal domain of E2 was involved in the suppressive effect. The relationship between STING, IFN-κ and interferon stimulated genes (ISGs) in HPK was confirmed by gene silencing and real time PCR. The expression of STING and IFN-κ were further determined in clinical specimens by real time PCR. STING and IFN-κ were down-modulated in HPV positive low grade squamous intraepithelial lesions compared with HPV negative controls. This study demonstrates that E2 proteins of high risk HPV reduce STING and IFN-κ transcription and its downstream target genes that might be an immune evasion mechanism involved in HPV persistence and cervical cancer development.

Aedes aegypti is the main vector of dengue globally. The variables that influence the abundance of dengue vectors are numerous and complex. This has generated a need to focus on areas at risk of disease transmission, the spatial-temporal distribution of vectors, and the factors that modulate vector abundance. To help guide and improve vector-control efforts, this study identified the ecological, social, and other environmental risk factors that affect the abundance of adult female and immature Ae. aegypti in households in urban and rural areas of northeastern Thailand. A one-year entomological study was conducted in four villages of northeastern Thailand between January and December 2019. Socio-demographic; self-reported prior dengue infections; housing conditions; durable asset ownership; water management; characteristics of water containers; knowledge, attitudes, and practices (KAP) regarding climate change and dengue; and climate data were collected. Household crowding index (HCI), premise condition index (PCI), socio-economic status (SES), and entomological indices (HI, CI, BI, and PI) were calculated. Negative binomial generalized linear models (GLMs) were fitted to identify the risk factors associated with the abundance of adult females and immature Ae. aegypti. Urban sites had higher entomological indices and numbers of adult Ae. aegypti mosquitoes than rural sites. Overall, participants’ KAP about climate change and dengue were low in both settings. The fitted GLM showed that a higher abundance of adult female Ae. aegypti was significantly (p < 0.05) associated with many factors, such as a low education level of household respondents, crowded households, poor premise conditions, surrounding house density, bathrooms located indoors, unscreened windows, high numbers of wet containers, a lack of adult control, prior dengue infections, poor climate change adaptation, dengue, and vector-related practices. Many of the above were also significantly associated with a high abundance of immature mosquito stages. The GLM model also showed that maximum and mean temperature with four-and one-to-two weeks of lag were significant predictors (p < 0.05) of the abundance of adult and immature mosquitoes, respectively, in northeastern Thailand. The low KAP regarding climate change and dengue highlights the engagement needs for vector-borne disease prevention in this region. The identified risk factors are important for the critical first step toward developing routine Aedes surveillance and reliable early warning systems for effective dengue and other mosquito-borne disease prevention and control strategies at the household and community levels in this region and similar settings elsewhere.

Dengue, a viral disease transmitted by Aedes mosquitoes, is an important public health concern throughout Thailand. Climate variables are potential predictors of dengue transmission. Associations between climate variables and dengue have usually been performed on large-scale first-level national administrative divisions, i.e. provinces. Here we analyze data on a finer spatial resolution in one province, which is often more relevant for effective disease control design. The objective of this study was to investigate the effect of seasonal variations, monthly climate variability, and to identify local clusters of symptomatic disease at the sub-district level based on reported dengue cases. Data on dengue cases were retrieved from the national communicable disease surveillance system in Thailand. Between 2006 and 2016, 15,167 cases were recorded in 199 sub-districts of Khon Kaen Province, northeastern Thailand. Descriptive analyses included demographic characteristics and temporal patterns of disease and climate variables. The association between monthly disease incidence and climate variations was analyzed at the sub-district level using Bayesian Poisson spatial regression. A hotspot analysis was used to assess the spatial patterns (clustered/dispersed/random) of dengue incidence. Dengue was predominant in the 5–14 year-old age group (51.1%). However, over time, dengue incidence in the older age groups (> 15 years) gradually increased and was the most affected group in 2013. Dengue outbreaks coincide with the rainy season. In the spatial regression model, maximum temperature was associated with higher incidence. The hotspot analysis showed clustering of cases around the urbanized area of Khon Kaen city and in rural areas in the southwestern portion of the province. There was an increase in the number of reported dengue cases in older age groups over the study period. Dengue incidence was highly seasonal and positively associated with maximum ambient temperature. However, climatic variables did not explain all the spatial variation of dengue in the province. Further analyses are needed to clarify the detailed effects of urbanization and other potential environmental risk factors. These results provide useful information for ongoing prediction modeling and developing of dengue early warning systems to guide vector control operations.

Dengue is linked with climate change in tropical and sub-tropical countries including the Lao People's Democratic Republic (Laos) and Thailand. Knowledge about these issues and preventive measures can affect the incidence and outbreak risk of dengue. Therefore, the present study was conducted to determine the knowledge, attitudes, and practices (KAP) among urban and rural communities and government officials about climate change and dengue in Laos and Thailand. A cross-sectional KAP survey about climate change and dengue were conducted in 360 households in Laos (180 urban and 180 rural), 359 households in Thailand (179 urban and 180 rural), and 20 government officials (10 in each country) using structured questionnaires. Data analysis was undertaken using descriptive methods, principal component analysis (PCA), Chi-square test or Fisher's exact test (as appropriate), and logistic regression. Significant differences among the selected communities in both countries were found in terms of household participant's age, level of education, socioeconomic status, attitude level of climate change and KAP level of dengue (P < 0.05; 95% CI). Overall, participants' KAP about climate change and dengue were low except the attitude level for dengue in both countries. The level of awareness among government officials regarding the climatic relationship with dengue was also low. In Lao households, participants' knowledge about climate change and dengue was significantly associated with the level of education and socioeconomic status (SES) (P < 0.01). Their attitudes towards climate change and dengue were associated with educational level and internet use (P < 0.05). Householders' climate change related practices were associated with SES (P < 0.01) and dengue related practices were associated with educational level, SES, previous dengue experience and internet use (P < 0.01). In Thailand, participants' knowledge about climate change was associated with the level of education and SES (P < 0.01). Their attitudes towards climate change were associated with residence status (urban/rural) and internet use (P < 0.05); climate change related practices were associated with educational level and SES (P < 0.05). Dengue related knowledge of participants was associated with SES and previous dengue experience (P < 0.05); participants' dengue related attitudes and practices were associated with educational level (P < 0.01). The findings call for urgently needed integrated awareness programs to increase KAP levels regarding climate change adaptation, mitigation and dengue prevention to improve the health and welfare of people in these two countries, and similar dengue-endemic countries.

Background: The variation of human papillomavirus (HPV) genes or HPV variants demonstrates different risks of cervical cancer. Mutation in the long control region (LCR) at YY1-motifs is one of the mechanisms for enhancing viral oncogene expression during the course of cancer cell progression. In Thai women, cervical cancers are almost always associated with HPV16 variant sub-lineage Asian (HPV16As); however, the mechanism involved remains elusive. The aim of this study was to understand further the oncogenic potential of HPV16As. Methods: A total of 82 HPV16-positive specimens from Thai women were selected from formalin-fixed paraffin-embedded cervical tissues, and the full length E6 gene of each specimen was amplified and sequenced. LCRs of the HPV16As-positive cases were amplified and sequenced to analyze their polymorphisms. Transcriptional activities of the HPV16As LCRs were then compared with sub-lineage European (EUR), sub-lineage Asian-American 1 (AA1) and HPV16 prototype by insertion of the LCRs into the pGL3-Basic vector. Results: The HPV16 DNA sequences were classified as HPV16 prototype (18.3%), Asian (As, 61%), Asian American-1 (AA1, 8.5%), European (EUR, 7.3%), Asian African-2 (AFR2, 3.7%) and Java-135C (J135C, 1.2%). The prevalence of HPV16As was 30% in low-grade squamous intraepithelial lesion (LSIL), while that in high-grade squamous intraepithelial lesion (HSIL) and squamous cell cervical carcinoma (SCC) were 63.9% and 66.7%, respectively, which demonstrates a significant association of HPV16As with the disease severity. LCR polymorphisms from 43 HPV16As positive cases were analyzed by PCR-sequencing. Thirty-eight nucleotide variation positions spanned nucleotide positions 7157–82. Ten new mutations found in the HPV16As LCRs were located predominantly at the enhancer and proximal to the 3’-end of the early promoter. The LCRs of the common HPV16As, EUR and AA1 showed 5, 13 and 23-fold higher activity than the HPV16 prototype LCR, while those of the new nucleotide variations of As showed 19 (As-sv1) and 30 (As-sv14) -fold higher activity than the HPV16 prototype. Conclusions: HPV16As DNA sequence variation, especially at the proximal to early promoter in the LCR, enhances transcriptional activity. This could be one of the possible mechanisms for HPV16As-associated cervical cancer development.

Background.Assessment of DNA methylation of specific genes is one approach to the diagnosis of cancer worldwide. Early stage detection is necessary to reduce the mortality rate of cancers, including those occurring in the stomach. For this purpose, tumor cells in circulating blood offer promising candidates for non-invasive diagnosis. Transcriptional inactivation of tumor suppressor genes, likePCDH10andRASSF1A, by methylation is associated with progression of gastric cancer, and such methylation can therefore be utilized as a biomarker.Methods.The present research was conducted to evaluate DNA methylation in these two genes using blood samples of gastric cancer cases. Clinicopathological data were also analyzed and cumulative survival rates generated for comparison.Results.High frequencies ofPCDH10andRASSF1Amethylations in the gastric cancer group were noted (94.1% and 83.2%, respectively, as compared to 2.97% and 5.45% in 202 matched controls). Most patients (53.4%) were in severe stage of the disease, with a median survival time of 8.4 months after diagnosis. Likewise, the patients with metastases, orRASSF1AandPCDH10methylations, had median survival times of 7.3, 7.8, and 8.4 months, respectively. A Kaplan–Meier analysis showed that cumulative survival was significantly lower in those cases positive for methylation ofRASSF1Athan in their negative counterparts. Similarly, whereas almost 100% of patients positive forPCDH10methylation had died after five years, none of the negative cases died over this period. Notably, the methylations ofRASSF1AandPCDH10were found to be higher in the late-stage patients and were also significantly correlated with metastasis and histology.Conclusions.PCDH10andRASSF1Amethylations in blood samples can serve as potential non-invasive diagnostic indicators in blood for gastric cancer. In addition toRASSF1Amethylation, tumor stage proved to be a major prognostic factor in terms of survival rates.