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Vascular permeability and plasma leakage are immune-pathologies of severe dengue virus (DENV) infection, but the mechanisms underlying the exacerbated inflammation during DENV pathogenesis are unclear. Here, we demonstrate that TLR2, together with its co-receptors CD14 and TLR6, is an innate sensor of DENV particles inducing inflammatory cytokine expression and impairing vascular integrity in vitro. Blocking TLR2 prior to DENV infection in vitro abrogates NF-κB activation while CD14 and TLR6 block has a moderate effect. Moreover, TLR2 block prior to DENV infection of peripheral blood mononuclear cells prevents activation of human vascular endothelium, suggesting a potential role of the TLR2-responses in vascular integrity. TLR2 expression on CD14 + + classical monocytes isolated in an acute phase from DENV-infected pediatric patients correlates with severe disease development. Altogether, these data identify a role for TLR2 in DENV infection and provide insights into the complex interaction between the virus and innate receptors that may underlie disease pathogenesis. The mechanisms underlying immunpathologies in dengue virus (DENV) infection are incompletely understood. Here, authors show that TLR2 recognizes DENV particles inducing cytokine expression and activating vascular endothelium cells in vitro, and that TLR2 expression on monocytes correlates with disease severity in patients.

Domestic violence against women remains a public health and socio-economic burden in Cambodia, with only slow declines over the past two decades. This study examined how digital access, media exposure, motorcycle ownership, and partners’ alcohol use are associated with intimate partner violence (IPV), defined as the experience of any sexual, physical, or emotional violence by a current or former partner within the past 12 months, adjusted for socio-demographic factors. A cross-sectional analysis of 5,780 weighted women aged 15–49 from the 2021–2022 Cambodia Demographic and Health Survey. IPV was regressed on mobile phone ownership, internet use, media exposure, motorcycle ownership, and partners’ alcohol use using survey-adjusted multivariable logistic models. Overall, 13.2% of women reported experiencing IPV in the past year, specifically emotional violence (12.2%), physical violence (4.4%), and sexual violence (1.9%). Smartphone ownership was associated with lower odds of emotional violence (AOR = 0.7; 95% CI 0.5–0.9) and IPV (AOR = 0.7; 95% CI: 0.5–1.0), whereas low-frequency internet use predicted higher odds of emotional violence (AOR = 1.7; 95% CI: 1.1–2.7) and IPV (AOR = 1.6; 95% CI: 1.1–2.5). Partner alcohol use was a strong risk factor for IPV (AOR = 3.0; 95% CI: 2.1–4.1 and all forms: sexual (AOR = 3.5; 95% CI: 1.1–11.4), physical (AOR = 5.6; 95% CI: 2.8–11.5), and emotional (AOR = 3.1; 95% CI: 2.2–4.4). Women in wealthier households had significantly lower odds of IPV (AOR = 0.6; 95% CI: 0.5–0.8), and specifically, physical violence (AOR = 0.4; 95% CI: 0.3–0.7). These findings highlight the dual role of digital inclusion—smartphones may enhance women’s protection, while limited or monitored internet access could heighten risk. Policies should be formulated to prioritize safe and private digital access, integrate gender-sensitive digital literacy, and strengthen alcohol control, and women’s economic empowerment within Cambodia’s National Action Plan to Prevent Violence Against Women 2019–2023 and forthcoming 2024–2030 framework.

Breast cancer incidence is increasing globally, and it is the third leading cause of morbidity and mortality among women in Cambodia. This study explores how access to digital tools, media exposure, transportation, travel time to health facilities, and autonomy in health decisions relate to breast cancer screening among Cambodian women aged 15–49. The study used nationally representative, cross-sectional data from the Cambodia Demographic and Health Survey (CDHS) 2021–2022. After excluding 204 women who were unaware of breast or cervical cancer screening, the final weighted sample comprised 19,292 participants. The outcome was whether a woman had ever received a breast examination from a healthcare provider, encompassing clinical breast examinations (CBEs) and imaging techniques, such as mammograms. Multivariable logistic regression, adjusted for demographic and socioeconomic characteristics, was used. Only 10.9% (95% CI: 9.7%–11.6%) of women had undergone a breast exam. Exposure to multiple forms of media was associated with a higher odds of screening (AOR = 1.47; 95% CI: 1.13–1.91). Phone ownership—both non-smartphone (AOR = 1.35; 95% CI: 1.03–1.78) or smartphone (AOR = 1.37; 95% CI: 1.03–1.82)—was also positively associated. In contrast, longer travel times of over 30 minutes (AOR = 0.55; 95% CI: 0.39–0.78) and a lack of autonomy in healthcare decisions (AOR = 0.70; 95% CI: 0.52–0.94) were associated with reduced screening. Wealthier women had greater odds of being screened (AOR = 1.86; 95% CI: 1.40–2.48). These findings highlight the need for health initiatives that use digital communication to reach and emphasize the importance of improving transportation, and support women’s decision-making to increase screening rates in Cambodia.

Dengue is an acute viral disease caused by dengue virus (DENV), which is transmitted by Aedes mosquitoes. Symptoms of DENV infection range from inapparent to severe and can be life-threatening. DENV replicates in primary immune cells such as dendritic cells and macrophages, which contribute to the dissemination of the virus. Susceptibility of other immune cells such as B cells to direct infection by DENV and their subsequent response to infection is not well defined. In a cohort of 60 Cambodian children, we showed that B cells are susceptible to DENV infection. Moreover, we show that B cells can support viral replication of laboratory adapted and patient-derived DENV strains. B cells were permissive to DENV infection albeit low titers of infectious virions were released in cell supernatants CD300a, a phosphatidylserine receptor, was identified as a potential attachment factor or receptor for entry of DENV into B cells. In spite of expressing Fc γ -receptors, antibody-mediated enhancement of DENV infection was not observed in B cells in an in vitro model. Direct infection by DENV induced proliferation of B cells in dengue patients in vivo and plasmablast/plasma cell formation in vitro . To summarize, our results show that B cells are susceptible to direct infection by DENV via CD300a and the subsequent B cell responses could contribute to dengue pathogenesis.

The clinical presentation of dengue virus (DENV) infection is variable. Severe complications mainly result from exacerbated immune responses. Type I interferons (IFN-I) are important in antiviral responses and form a crucial link between innate and adaptive immunity. Their contribution to host defense during DENV infection remains under-studied, as direct quantification of IFN-I is challenging. We combined ultra-sensitive single-molecule array (Simoa) digital ELISA with IFN-I gene expression to elucidate the role of IFN-I in a well-characterized cohort of hospitalized Cambodian children undergoing acute DENV infection. Higher concentrations of type I IFN proteins were observed in blood of DENV patients, compared to healthy donors, and correlated with viral load. Stratifying patients for disease severity, we found a decreased expression of IFN-I in patients with a more severe clinical outcome, such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). This was seen in parallel to a correlation between low IFNα protein concentrations and decreased platelet counts. Type I IFNs concentrations were correlated to frequencies of plasmacytoid DCs, not DENV-infected myloid DCs and correlated inversely with neutralizing anti-DENV antibody titers. Hence, type I IFN produced in the acute phase of infection is associated with less severe outcome of dengue disease.

Dengue is a mosquito-borne viral disease caused by dengue virus (DENV). The disease is endemic to more than 100 countries with 390 million dengue infections per year. Humoral immune responses during primary and secondary DENV infections are well-investigated. However, the impact of DENV infection on B cell subsets and their antibody-independent functions are not well-documented. Through this study, we aimed to define the distribution of B cell subsets in the acute phase of DENV infection and characterize the effect of DENV infection on B cell functions such as differentiation into memory and plasma cells and cytokine production. In our cohort of Cambodian children, we observed decreased percentages of CD24 CD38 B cells and CD27 naïve B cells within the CD19 population and increased percentages of CD27 CD38 CD138 plasma cells as early as 4 days post appearance of fever in patients with severe dengue compared to patients with mild disease. Lower percentages of CD19 CD24 CD38 B cells in DENV-infected patients were associated with decreased concentrations of soluble CD40L in patient plasma and decreased platelet counts in these patients. In addition, CD19 CD24 CD38 and CD19 CD27 B cells from DENV-infected patients did not produce IL-10 or TNF-α upon stimulation , suggesting their contribution to an altered immune response during DENV infection. In addition, CD19 CD27 naïve B cells isolated from dengue patients were refractory to TLR/anti-IgM stimulation , which correlated to the increased expression of inhibitory Fcγ receptors (FcγR) CD32 and LILRB1 on CD19 CD27 naïve B cells from DENV-infected patients. Collectively, our results indicate that a defective B cell response in dengue patients may contribute to the pathogenesis of dengue during the early phase of infection.

Human enterovirus 71 (EV-A71) causes hand, foot and mouth disease (HFMD). EV-A71 circulates in many countries and has caused large epidemics, especially in the Asia-Pacific region, since 1997. In April 2012, an undiagnosed fatal disease with neurological involvement and respiratory distress occurred in young children admitted to the Kantha Bopha Children's Hospital in Phnom Penh, Cambodia. Most died within a day of hospital admission, causing public panic and international concern. In this study, we describe the enterovirus (EV) genotypes that were isolated during the outbreak in 2012 and the following year. From June 2012 to November 2013, 312 specimens were collected from hospitalized and ambulatory patients and tested by generic EV and specific EV-A71 reverse transcription PCR. EV-A71 was detected in 208 clinical specimens while other EVs were found in 32 patients. The VP1 gene and/or the complete genome were generated. Our phylogenetic sequencing analysis demonstrated that 80 EV-A71 strains belonged to the C4a subgenotype and 3 EV-A71 strains belonged to the B5 genotype. Furthermore, some lineages of EV-A71 were found to have appeared in Cambodia following separate introductions from neighboring countries. Nineteen EV A (CV-A6 and CV-A16), 9 EV B (EV-B83, CV-B3, CV-B2, CV-A9, E-31, E-2 and EV-B80) and 4 EV C (EV-C116, EV-C96, CV-A20 and Vaccine-related PV-3) strains were also detected. We found no molecular markers of disease severity. We report here that EV-A71 genotype C4 was the main etiological agent of a large outbreak of HFMD and particularly of severe forms associated with central nervous system infections. The role played by other EVs in the epidemic could not be clearly established.

Acute meningoencephalitis (AME) is associated with considerable morbidity and mortality in children in developing countries. Clinical specimens were collected from children presenting with AME at two Cambodian paediatric hospitals to determine the major aetiologies associated with AME in the country. Cerebrospinal fluid (CSF) and blood samples were screened by molecular and cell culture methods for a range of pathogens previously associated with AME in the region. CSF and serum (acute and convalescent) were screened for antibodies to arboviruses such as Japanese encephalitis virus (JEV), dengue virus (DENV), and chikungunya virus (CHIKV). From July 2010 through December 2013, 1160 children (one month to 15 years of age) presenting with AME to two major paediatric hospitals were enroled into the study. Pathogens associated with AME were identified using molecular diagnostics, cell culture and serology. According to a diagnostic algorithm, a confirmed or highly probable aetiologic agent was detected in 35.0% (n=406) of AME cases, with a further 9.2% (total: 44.2%, n=513) aetiologies defined as suspected. JEV (24.4%, n=283) was the most commonly identified pathogen followed by Orientia tsutsugamushi (4.7%, n=55), DENV (4.6%, n=53), enteroviruses (3.5%, n=41), CHIKV (2.0%, n=23) and Streptococcus pneumoniae (1.6%, n=19). The majority of aetiologies identified for paediatric AME in Cambodia were vaccine preventable and/or treatable with appropriate antimicrobials. Emerging Microbes & Infections (2017) 6, e35; doi: 10.1038/emi.2017.15 ; published online 24 May 2017

We examined the prevalence of low birth weight (LBW) across provinces and factors associated with LBW among newborns in Cambodia. We analyzed the most recent children's data from the 2021-2022 Cambodia Demographic and Health Survey (CDHS). A total of 4565 weighted newborns were included in the study. Provincial variation in the prevalence of LBW was visualized using ArcGIS. Multiple logistic regression analyses were performed to identify factors associated with LBW. The prevalence of LBW was 5.9% (95% CI: 5.2-6.8), with the highest rates observed in Ratanak Kiri (13.9%), Kratie (12.8%), Pailin (12.7%), and Svay Rieng (10.2%). After adjusting for confounders, significant factors associated with higher odds of LBW included maternal unemployment (AOR = 1.62; 95% CI: 1.03-2.56), being a first-born child (AOR = 1.73; 95% CI: 1.26-2.38), and rural area (AOR = 1.41; 95% CI: 1.00-2.01). Attending four or more antenatal care (ANC) visits was protective against LBW (AOR = 0.65; 95% CI: 0.47-0.91). Maternal age and household wealth were not independently associated with LBW in the adjusted model. The prevalence of LBW among newborns in Cambodia is lower than in Southeast Asia and worldwide. However, significant provincial variations in LBW prevalence exist, particularly in remote areas. Maternal employment, firstborn status, rural residence, and ANC utilization are key determinants of LBW. Public health programs should prioritize provinces with persistently high rates of LBW prevalence and improve ANC coverage, especially for first-time mothers in rural areas, to further reduce LBW and improve neonatal outcomes.

Domestic violence against women remains a public health and socio-economic burden in Cambodia, with only slow declines over the past two decades. This study examined how digital access, media exposure, motorcycle ownership, and partners' alcohol use are associated with intimate partner violence (IPV), defined as the experience of any sexual, physical, or emotional violence by a current or former partner within the past 12 months, adjusted for socio-demographic factors. A cross-sectional analysis of 5,780 weighted women aged 15-49 from the 2021-2022 Cambodia Demographic and Health Survey. IPV was regressed on mobile phone ownership, internet use, media exposure, motorcycle ownership, and partners' alcohol use using survey-adjusted multivariable logistic models. Overall, 13.2% of women reported experiencing IPV in the past year, specifically emotional violence (12.2%), physical violence (4.4%), and sexual violence (1.9%). Smartphone ownership was associated with lower odds of emotional violence (AOR = 0.7; 95% CI 0.5-0.9) and IPV (AOR = 0.7; 95% CI: 0.5-1.0), whereas low-frequency internet use predicted higher odds of emotional violence (AOR = 1.7; 95% CI: 1.1-2.7) and IPV (AOR = 1.6; 95% CI: 1.1-2.5). Partner alcohol use was a strong risk factor for IPV (AOR = 3.0; 95% CI: 2.1-4.1 and all forms: sexual (AOR = 3.5; 95% CI: 1.1-11.4), physical (AOR = 5.6; 95% CI: 2.8-11.5), and emotional (AOR = 3.1; 95% CI: 2.2-4.4). Women in wealthier households had significantly lower odds of IPV (AOR = 0.6; 95% CI: 0.5-0.8), and specifically, physical violence (AOR = 0.4; 95% CI: 0.3-0.7). These findings highlight the dual role of digital inclusion-smartphones may enhance women's protection, while limited or monitored internet access could heighten risk. Policies should be formulated to prioritize safe and private digital access, integrate gender-sensitive digital literacy, and strengthen alcohol control, and women's economic empowerment within Cambodia's National Action Plan to Prevent Violence Against Women 2019-2023 and forthcoming 2024-2030 framework.