Structure, Regulation, and Significance of Cyanobacterial and Chloroplast Adenosine Triphosphate Synthase in the Adaptability of Oxygenic Photosynthetic Organisms.

In cyanobacteria and chloroplasts (in algae and plants), ATP synthase plays a pivotal role as a photosynthetic membrane complex responsible for producing ATP from adenosine diphosphate and inorganic phosphate, utilizing a proton motive force gradient induced by photosynthesis. These two ATP synthases exhibit similarities in gene organization, amino acid sequences of subunits, structure, and functional mechanisms, suggesting that cyanobacterial ATP synthase is probably the evolutionary precursor to chloroplast ATP synthase. In this review, we explore the precise synthesis and assembly of ATP synthase subunits to address the uneven stoichiometry within the complex during transcription, translation, and assembly processes. We also compare the regulatory strategies governing ATP synthase activity to meet varying energy demands in cyanobacteria and chloroplasts amid fluctuating natural environments. Furthermore, we delve into the role of ATP synthase in stress tolerance and photosynthetic carbon fixation efficiency in oxygenic photosynthetic organisms (OPsOs), along with the current researches on modifying ATP synthase to enhance carbon fixation efficiency under stress conditions. This review aims to offer theoretical insights and serve as a reference for understanding the functional mechanisms of ATP synthase, sparking innovative ideas for enhancing photosynthetic carbon fixation efficiency by utilizing ATP synthase as an effective module in OPsOs.

Feasibility of monitoring Global Breast Cancer Initiative Framework key performance indicators in 21 Asian National Cancer Centers Alliance member countries.

Background: The Global Breast Cancer Initiative (GBCI) Framework, launched by the World Health Organisation (WHO) in 2023, emphasises assessing, strengthening, and scaling up services for the early detection and management of breast cancer. This study aims to determine the feasibility of monitoring the status of breast cancer control in the 21 Asian National Cancer Centers Alliance (ANCCA) countries based on the three GBCI Framework key performance indicators (KPIs): stage at diagnosis, time to diagnosis, and treatment completion. Methods: We reviewed published literature on breast cancer control among 21 ANCCA countries from May to July 2023 to establish data availability and compiled the latest descriptive statistics and sources of the indicators using a standardised data collection form. We performed bivariate Pearson's correlation analysis to measure the strength of correlation between stage at diagnosis, mortality and survival rates, and universal health coverage. Findings: Only 12 (57%) ANCCA member countries published national cancer registry reports on breast cancer age-standardised incidence rate (ASIR) and age-standardised mortality rate (ASMR). Indonesia, Myanmar, and Nepal had provincial data and others relied on WHO's Global Cancer Observatory (GLOBOCAN) estimates. GLOBOCAN data differed from the reported national statistics by 5-10% in Bhutan, Indonesia, Iran, the Republic of Korea, Singapore, and Thailand and >10% in China, India, Malaysia, Mongolia, and Sri Lanka. The proportion of patients diagnosed in stages I and II strongly correlated with the five-year survival rate and with the universal health coverage (UHC) index. Three countries (14%) reported national data with >60% of invasive breast cancer patients diagnosed at stages I and II, and a five-year survival rate of >80%. Over 60% of the ANCCA countries had no published national data on breast cancer staging, the time interval from presentation to diagnosis, and diagnosis to treatment. Five (24%) countries reported data on treatment completion. The definition of delayed diagnosis and treatment completion varied across countries. Interpretation: GBCI's Pillar 1 KPI correlates strongly with five-year survival rate and with the UHC index. Most ANCCA countries lacked national data on cancer staging, timely diagnosis, and treatment completion KPIs. While institutional-level data were available in some countries, they may not represent the nationwide status. Strengthening cancer surveillance is crucial for effective breast cancer control. The GBCI Framework indicators warrant more detailed definitions for standardised data collection. Surrogate indicators which are measurable and manageable in country-specific settings, could be considered for monitoring GBCI indicators. Ensuring UHC and addressing health inequalities are essential to early diagnosis and treatment of breast cancer. Funding: Funding for this research article's processing fee (APC) will be provided by the affiliated institution to support the open-access publication of this work. The funding body is not involved in the study design; collection, management, analysis and interpretation of data; or the decision to submit for publication. The funding body will be informed of any planned publications, and documentation provided.

Progress towards the 2020 milestones of the end TB strategy in Cambodia: estimates of age and sex specific TB incidence and mortality from the Global Burden of Disease Study 2019.

BACKGROUND: Cambodia was recently removed from the World Health Organization's (WHO's) top 30 high tuberculosis (TB) burden countries. However, Cambodia's TB burden remains substantial, and the country is on the WHO's new global TB watchlist. We aimed to examine the levels and trends in the fatal and non-fatal TB burden in Cambodia from 1990 to 2019, assessing progress towards the WHO End TB interim milestones, which aim to reduce TB incidence rate by 20% and TB deaths by 35% from 2015 to 2020. METHODS: We leveraged the Global Burden of Disease 2019 (GBD 2019) analytical framework to compute age- and sex-specific TB mortality and incidence by HIV status in Cambodia. We enumerated TB mortality utilizing a Bayesian hierarchical Cause of Death Ensemble modeling platform. We analyzed all available data sources, including prevalence surveys, population-based tuberculin surveys, and TB cause-specific mortality, to produce internally consistent estimates of incidence and mortality using a compartmental meta-regression tool (DisMod-MR 2.1). We further estimated the fraction of tuberculosis mortality among individuals without HIV coinfection attributable to the independent effects of alcohol use, smoking, and diabetes. RESULTS: In 2019, there were 6500 (95% uncertainty interval 4830-8680) deaths due to all-form TB and 50.0 (43.8-57.8) thousand all-form TB incident cases in Cambodia. The corresponding age-standardized rates were 53.3 (39.9-69.4) per 100,000 population for mortality and 330.5 (289.0-378.6) per 100,000 population for incidence. From 2015 to 2019, the number of all-form TB deaths decreased by 11.8% (2.3-21.1), while the age-standardized all-form TB incidence rate decreased by 11.1% (6.3-15.6). Among individuals without HIV coinfection in 2019, alcohol use accounted for 28.1% (18.2-37.9) of TB deaths, smoking accounted for 27.0% (20.2-33.3), and diabetes accounted for 12.5% (7.1-19.0). Removing the combined effects of these risk factors would reduce all-form TB deaths by 54.2% (44.2-62.2). DISCUSSION: Despite significant progress in reducing TB morbidity and mortality since 1990, Cambodia is not on track to achieve the 2020 WHO End TB interim milestones. Existing programs in Cambodia can benefit from liaising with risk factor control initiatives to accelerate progress toward eliminating TB in Cambodia.

Developing a toolkit for implementing evidence-based guidelines to manage hypertension and diabetes in Cambodia: a descriptive case study.

BACKGROUND: In Cambodia, economic development accompanied by health reforms has led to a rapidly ageing population and an increasing incidence and prevalence of noncommunicable diseases. National strategic plans recognize primary care health centres as the focal points of care for treating and managing chronic conditions, particularly hypertension and type 2 diabetes. However, health centres have limited experience in providing such services. This case study describes the process of developing a toolkit to facilitate the use of evidence-based guidelines to manage hypertension and type 2 diabetes at the health-centre level. METHODS: We developed and revised a preliminary toolkit based on the feedback received from key stakeholders. We gathered feedback through an iterative process of group and one-to-one consultations with representatives of the Ministry of Health, provincial health department, health centres and nongovernmental organizations between April 2019 and March 2021. RESULTS: A toolkit was developed and organized according to the core tasks required to treat and manage hypertension and type 2 diabetes patients. The main tools included patient identification and treatment cards, risk screening forms, a treatment flowchart, referral forms, and patient education material on risk factors and lifestyle recommendations on diet, exercise, and smoking cessation. The toolkit supplements existing guidelines by incorporating context-specific features, including drug availability and the types of medication and dosage guidelines recommended by the Ministry of Health. Referral forms can be extended to incorporate engagement with community health workers and patient education material adapted to the local context. All tools were translated into Khmer and can be modified as needed based on available resources and arrangements with other institutions. CONCLUSIONS: Our study demonstrates how a toolkit can be developed through iterative engagement with relevant stakeholders individually and in groups to support the implementation of evidence-based guidelines. Such toolkits can help strengthen the function and capacity of the primary care system to provide care for noncommunicable diseases, serving as the first step towards developing a more comprehensive and sustainable health system in the context of population ageing and caring for patients with chronic diseases.

Economic Evaluation of Community Tuberculosis Active Case-Finding Approaches in Cambodia: A Quasi-Experimental Study.

This study aimed to estimate the costs and incremental cost-effectiveness of two community-based tuberculosis (TB) active case-finding (ACF) strategies in Cambodia. We also assessed the number needed to screen and test to find one TB case. Program and national TB notification data from a quasi-experimental study of a cohort of people with TB in 12 intervention operational districts (ODs) and 12 control ODs between November 2018 and December 2019 were analyzed. Two ACF interventions (ACF seed-and-recruit (ACF SAR) model and one-off roving (one-off) ACF) were implemented concurrently. The matched control sites included PCF only. We estimated costs using the program and published data in Cambodia. The primary outcome was disability-adjusted life years (DALY) averted over 14 months. We considered the gross domestic product per capita of Cambodia in 2018 as the cost-effectiveness threshold. ACF SAR needed to test 7.7 people with presumptive TB to identify one all-forms TB, while one-off ACF needed to test 22.4. The costs to diagnose one all-forms TB were USD 458 (ACF SAR) and USD 191 (one-off ACF). The incremental cost per DALY averted was USD 257 for ACF SAR and USD 204 for one-off ACF. Community-based ACF interventions that targeted key populations for TB in Cambodia were highly cost-effective.

Bibliometrics of Cambodian Science: subjects, researchers and impact in the Science Citation Index Expanded / Bibliometría de la ciencia camboyana: temas, investigadores e impacto en el Science Citation Index Expanded

Abstract Introduction: Cambodia is a small agricultural tropical country for which only two small scientometric studies, published five years ago, were available until now. Objective: To identify, for Cambodian research, subjects, outlets, authors, institutions, citations and recommendations. Methods: The data were retrieved from the Science Citation Index Expanded (January 04, 2021) using the word "Cambodia" for the period 1972 to 2019. Results: We retrieved 3 689 documents: for the half century covered, the yearly presence of Cambodia in the index has grown strongly, to 325 articles and 6 555 authors in 2019 alone. Most documents are articles in English about health, particularly infectious and tropical diseases. Most international collaboration is done, by country, with the USA, France, and Thailand; and by institution, with Mahidol University, the Pasteur Institute and Oxford University. The most productive institutions are the Cambodian Ministry of Health and the Cambodian National Center for Parasitology. The main outlets are PLoS One, Malaria and PLoS Neglected Tropical Diseases. Cambodian articles are cited for up to 33 years, with a peak of 4.5 citations within the first two years. Those in English, or from well-funded foreign projects, have more citations in this particular index; especially if they are about malaria, hepatitis or influenza. Conclusions: The nature and impact of Cambodian science outside the SCI-EXPANDED remain unknown, but publications in that index have increased, concentrate on solving local problems, and depend heavily on international collaboration, following a well-known pattern of science in tropical countries. We suggest a funding system based on international peers who assign funds to the most productive researchers with minimal bureaucracy, so that local research is done on a greater variety of topics and with less participation of Cambodian researchers as low-level members in foreign projects.

Resumen Introducción: Camboya es un país tropical asiático pequeño y "subdesarrollado", con una economía basada en la agricultura, para el que hasta ahora solo estaban disponibles dos pequeños estudios cienciométricos, publicados hace cinco años. Objetivo: Identificar, para la investigación camboyana, qué se estudia; quién hizo la investigación; dónde y cuándo se publicó; y los factores que afectan su citación. Métodos: Usamos el Science Citation Index Expanded (4 de enero de 2021) utilizando la palabra "Camboya" y se limitaron al período 1972 a 2019. Resultados: Hallamos 3 689 documentos; durante el medio siglo cubierto, la presencia anual de Camboya en el índice ha aumentado considerablemente, con 325 artículos y 6 555 autores incorporados tan solo en 2019. La mayoría son artículos en inglés sobre salud, particularmente enfermedades infecciosas y tropicales. La mayor parte de la colaboración internacional se realiza, por país, con EE. UU., Francia y Tailandia; y por institución, con la Universidad Mahidol, el Instituto Pasteur y la Universidad de Oxford. Las instituciones más productivas son el Ministerio de Salud de Camboya y el Centro Nacional de Parasitología de Camboya. Las principales revistas son PLoS One, Malaria y PLoS Neglected Tropical Diseases. Los artículos camboyanos se citan hasta por 33 años, con un máximo de 4.5 citas en los dos primeros años. Los que son en inglés, o de proyectos dirigidos por el extranjero, tienen más citas en esta base de datos; particularmente si se trata de malaria, hepatitis o influenza. Conclusiones: La naturaleza y el impacto de la ciencia camboyana fuera del SCI-EXPANDED siguen sin conocerse, pero las publicaciones en ese índice han aumentado, se concentran en resolver problemas locales y dependen en gran medida de la colaboración internacional, siguiendo un patrón bien conocido en los países tropicales. Sugerimos un sistema de financiación basado en pares internacionales que asignen, con burocracia mínima, fondos a los investigadores más productivos, de modo que la investigación local se realice en una mayor variedad de temas y con una menor participación de investigadores camboyanos como miembros de bajo nivel en proyectos extranjeros.

Risk factors of HIV infection among female entertainment workers in Cambodia: Findings of a national survey.

BACKGROUND: Cambodia has been well recognized for its success in the fight against the HIV epidemic. However, challenges remain in eliminating HIV infections in key populations, including women working in entertainment establishments, such as massage parlors, karaoke bars, or beer gardens. This study explored the prevalence of HIV and identified factors associated with HIV infection among female entertainment workers (FEWs) in Cambodia. METHODS: This national biological and behavioral survey was conducted in 2016 in Phnom Penh and 17 provinces. We used a two-stage cluster sampling method to recruit FEWs for HIV testing performed on-site and face-to-face interviews using a structured questionnaire. We investigated factors associated with HIV infection using multiple logistic regression. RESULTS: This study included 3149 FEWs with a mean age of 26.2 years (SD 5.7). The adjusted prevalence of HIV was 3.2% (95% CI 1.76-5.75). In the multiple logistic regression model, the odds of HIV infection were significantly higher among FEWs in the age group of 31 to 35 (AOR 2.72, 95% CI 1.36-8.25) and 36 or older (AOR 3.62, 95% CI 1.89-10.55); FEWs who were not married but living with a sexual partner (AOR 3.00, 95% CI 1.16-7.79); FEWs who had at least ten years of formal education (AOR 0.32, 95% CI 0.17-0.83); FEWs who reported having abnormal vaginal discharge (AOR 3.51, 95% CI 1.12-9.01), genital ulcers or sores (AOR 2.06, 95% CI 1.09-3.17), and genital warts (AOR 2.89, 95% CI 1.44-6.33) in the past three months; and FEWs who reported using illicit drugs (AOR 3.28, 95% CI 1.20-4.27) than their respective reference group. The odds of HIV infection were significantly lower among FEWs working in karaoke bars (AOR 0.26, 95% CI 0.14-0.50) and beer gardens (AOR 0.17, 95% CI 0.09-0.54) than among freelance FEWs. CONCLUSIONS: The prevalence of HIV among FEWs in Cambodia remains much higher than that in the general population. These findings indicate that differentiated strategies to address HIV and other sexually transmitted infections should be geared towards FEWs working as freelancers or in veiled entertainment venues such as massage parlors and freelance sex workers. Prevention efforts among venue-based FEWs should be sustained.

HIV risks and recent HIV testing among transgender women in Cambodia: Findings from a national survey.

BACKGROUND: Globally, the prevalence of HIV among transgender women remains much higher than that of the general population, and a large proportion of them are unaware of their HIV status. Transgender women are exposed to gender-based violence and social stigma and discrimination in different settings that may create significant barriers to receiving HIV prevention and care services. This study aimed to identify factors associated with recent HIV testing among transgender women in Cambodia. METHODS: We conducted a cross-sectional survey in 2016 among 1375 transgender women recruited from 13 provinces using a peer-based social network recruitment method. We used a structured questionnaire for face-to-face interviews and performed rapid HIV/syphilis testing onsite. We used a multiple logistic regression analysis to identify factors associated with recent HIV testing. RESULTS: Of the total, 49.2% of the participants reported having an HIV test in the past six months. After controlling for other covariates, the odds of having an HIV test in the past six months was significantly lower among students (AOR 0.36, 95% CI 0.20-0.65), participants who perceived that they were unlikely to be HIV infected (AOR 0.50, 95% CI 0.32-0.78), and participants who reported always using condoms with male non-commercial partners in the past three months (AOR 0.65, 95% CI 0.49-0.85) relative to their respective reference group. The odds of having an HIV test in the past six months was significantly higher among participants who had been reached by community-based HIV services (AOR 5.01, 95% CI 3.29-7.65) and received HIV education (AOR 1.65, 95% CI 1.06-2.58) in the past six months relative to their respective reference group. CONCLUSIONS: Despite the widely available free HIV testing services, more than half of transgender women in this study had not received an HIV test in the past six months. Our findings suggest that a tailored and comprehensive combination prevention program, in which HIV testing is linked to care continuum and beyond, maybe an essential next step. Social media may have the potential to be promoted and utilized among transgender women populations in order to improve HIV testing and other prevention measures.

Nutritional status and dietary diversity of school-age children living with HIV: a cross-sectional study in Phnom Penh, Cambodia.

BACKGROUND: HIV/AIDS continues to be a major public health concern for children. Each day, worldwide, approximately 440 children became newly infected with HIV, and 270 children died from AIDS-related causes in 2018. Poor nutrition has been associated with accelerated disease progression, and sufficient dietary diversity is considered a key to improve children's nutritional status. Therefore, this study aims to 1) examine nutritional status of school-age children living with HIV in Phnom Penh, Cambodia, and 2) identify factors associated with their nutritional status, especially taking their dietary diversity into consideration. METHODS: This cross-sectional study was conducted in May 2018 within the catchment area of the National Pediatric Hospital, Cambodia. Data from 298 children and their caregivers were included in the analyses. Using semi-structured questionnaires, face-to-face interviews were conducted to collect data regarding sociodemographic characteristics, quality of life, and dietary diversity. To assess children's nutritional status, body weight and height were measured. Viral load and duration of antiretroviral therapy (ART) were collected from clinical records. Multiple logistic regression analyses were performed to identify factors associated with stunting and wasting. RESULTS: Of 298 children, nearly half (46.6%) were stunted, and 13.1% were wasted. The mean number of food groups consumed by the children in the past 24 h was 4.6 out of 7 groups. Factors associated with children's stunting were age (adjusted odds ratio [AOR] 2.166, 95% confidence interval [CI]: 1.151, 4.077), household wealth (AOR 0.543, 95%CI: 0.299, 0.986), duration of receiving ART (AOR 0.510, 95%CI: 0.267, 0.974), and having disease symptoms during the past 1 year (AOR 1.871, 95%CI: 1.005, 3.480). The only factor associated with wasting was being male (AOR 5.304, 95%CI: 2.210, 12.728). CONCLUSIONS: Prevalence of stunting was more than double that of non-infected school-age children living in urban areas in Cambodia. This highlights the importance of conducting nutritional intervention programs, especially tailored for children living with HIV in the country. Although dietary diversity was not significantly associated with children's nutritional status in this study, the findings will contribute to implementing future nutritional interventions more efficiently by indicating children who are most in need of such interventions in Cambodia.

Health Behaviors among Male and Female University Students in Cambodia: A Cross-Sectional Survey.

Students go through a transition when they enter university, which involves major individual and contextual changes in every domain of life that may lead to several behavioral and health problems. This study examined a wide range of health behaviors and practices among 1,359 male and female students recruited from two public universities in Cambodia using a multistage cluster sampling method. Health-related information in different domains were collected using a structured questionnaire. We compared the variables in male and female students. Of the total, 50.8% were male and the mean age was 21.3 (SD = 2.3) years. The majority (79.5%) reported not having any vigorous-intensity activities, 25.9% not having moderate-intensity activities, and 33.5% not having walked continuously for 10 min over the last week. More than one-third (38.3%) reported drinking alcohol, 1.1% smoking tobacco, and 0.4% using an illicit drug in the past 12 months. About one in ten (10.6%) reported having sexual intercourse; of whom, 42.4% reported not using a condom in the last intercourse, and the mean number of sexual partners was 2.1 (SD = 2.4) in the past 12 months. Only 7.1% reported having been diagnosed with a sexually transmitted infection (STI) in the past 12 months; of whom, 60% sought for treatment for the most recent STI. About one-third (33.6%) reported eating fast food at least once over the last week. More than half (55.6%) had one to two servings of fruits or vegetables daily, and 9.9% did not eat any fruits or vegetables over the last week. Gender differences were observed in physical activities, dietary intakes, cigarette smoking, alcohol drinking, and sexual behaviors. Findings from this study indicate that public health and education policies should promote healthy behaviors among university students. The interventions may take advantage of and expand upon the positive health behaviors and consider gender differences.

Effect of community active case-finding strategies for detection of tuberculosis in Cambodia: study protocol for a pragmatic cluster randomized controlled trial.

BACKGROUND: Cambodia has made notable progress in the fight against tuberculosis (TB). However, these gains are impeded by a significant proportion of undiagnosed cases. To effectively reach people with TB, active case-finding (ACF) strategies have been adopted by countries affected by the epidemic, including Cambodia, alongside passive case finding (PCF). Despite increased efforts to improve case detection, approximately 40% of TB cases in Cambodia remained undiagnosed in 2018. In Cambodia, several community-based TB ACF modalities have been implemented, but their effectiveness has yet to be systematically assessed. METHODS: This pragmatic cluster randomized controlled trial will be conducted between December 2019 and June 2021. We will randomize eight operational districts (clusters) in seven provinces (Kampong Cham, Kampong Thom, Prey Veng, Thbong Khmum, Kampong Chhnang, Kandal, and Kampong Speu) to either the control group (PCF) or the intervention groups (ACF using a seed-and-recruit model, ACF targeting household and neighborhood contacts, and ACF targeting persons aged ≥ 55 years using mobile screening units). The primary endpoints will be TB case notification rates, additionality, and cumulative yield of TB cases. The secondary endpoints include treatment outcomes, the number needed to screen to find one TB case, and cost-effectiveness outcome measures. We will analyze the primary and secondary endpoints by intention to treat. We will compare cluster and individual-level characteristics using Student's t test and hierarchical or mixed-effect models to estimate the ratio of these means. The incremental cost-effectiveness ratio per disability-adjusted life year averted will also be considered as a benchmark to determine whether the interventions are cost-effective. DISCUSSION: This study will build an evidence base to inform future scale-up, implementation, and sustainability of ACF strategies in Cambodia and other similar settings. Implementation of this study will also complement TB control strategies in Cambodia by conducting ACF in operational districts without active interventions to find TB cases currently. Those who are ill and might have TB will be promptly screened, diagnosed, and linked to care. Early diagnosis and treatment initiation will also benefit their community by interrupting transmission and prevent further infections. The experience gained from this project will inform future attempts in conducting pragmatic trials in low-resource settings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04094350. Registered on 18 September 2019.

Outcomes of HIV treatment from the private sector in low-income and middle-income countries: a systematic review protocol.

INTRODUCTION: Private sector provision of HIV treatment is increasing in low-income and middle-income countries (LMIC). However, there is limited documentation of its outcomes. This protocol reports a proposed systematic review that will synthesise clinical outcomes of private sector HIV treatment in LMIC. METHODS AND ANALYSIS: This review will be conducted in accordance with the preferred reporting items for systematic review and meta-analyses protocols. Primary outcomes will include: (1) proportion of eligible patients initiating antiretroviral therapy (ART); (2) proportion of those on ART with <1000 copies/mL; (3) rate of all-cause mortality among ART recipients. Secondary outcomes will include: (1) proportion receiving Pneumocystis jiroveci pneumonia prophylaxis; (2) proportion with >90% ART adherence (based on any measure reported); (3) proportion screened for non-communicable diseases (specifically cervical cancer, diabetes, hypertension and mental ill health); (iv) proportion screened for tuberculosis. A search of five electronic bibliographical databases (Embase, Medline, PsychINFO, Web of Science and CINAHL) and reference lists of included articles will be conducted to identify relevant articles reporting HIV clinical outcomes. Searches will be limited to LMIC. No age, publication date, study-design or language limits will be applied. Authors of relevant studies will be contacted for clarification. Two reviewers will independently screen citations and abstracts, identify full text articles for inclusion, extract data and appraise the quality and bias of included studies. Outcome data will be pooled to generate aggregative proportions of primary and secondary outcomes. Descriptive statistics and a narrative synthesis will be presented. Heterogeneity and sensitivity assessments will be conducted to aid interpretation of results. ETHICS AND DISSEMINATION: The results of this review will be disseminated through a peer-reviewed scientific manuscript and at international scientific conferences. Results will inform quality improvement strategies, replication of identified good practices, potential policy changes, and future research. PROSPERO REGISTRATION NUMBER: CRD42016040053.

Using participatory methods to build an mHealth intervention for female entertainment workers in Cambodia: the development of the Mobile Link project.

BACKGROUND: The HIV epidemic in Cambodia is strongly and disproportionately concentrated among key populations. One important hard-to-reach key population is the expanding community of female entertainment workers (FEWs). HIV as well as other sexual and reproductive health (SRH) outcomes including sexually transmitted infections (STIs), contraception, and gynecologic health are also substandard among FEWs. To address these concerns, a mobile health intervention (mHealth) using short message service (SMS) and voice message (VM) services-the Mobile Link project-was constructed. This paper aims to describe the development of this mHealth intervention that used participatory methodologies and to illustrate how these findings can be useful in future mHealth projects. METHODS: This intervention development process used an iterative, participatory approach. Twenty-seven focus group discussions (FGDs) covering SRH topics were designed and conducted and implemented across four provinces in Cambodia. Additionally, six in-depth interviews (IDIs) were conducted with FEWs living with HIV in Siem Reap and Phnom Penh. Data from the FGDs and IDIs were analyzed using content and matrix analysis methods to identify prioritized themes for messages. Two data validation workshops were organized to present the prioritized themes to FEWs and outreach workers (outreach workers) for validation. The workshops included activities stimulating participation such as listening to sample messages in order to determine health priorities as well as message tone and style. RESULTS: The findings from the qualitative research provided guidance on how to tailor the intervention to the FEW community in terms of the tone, timing, content and delivery mode of the messages. Participants preferred a friendly, professional female voice for VM. Participants revealed that health priorities such as gynecologic issues (vaginal infections/irritation) and cervical and breast cancer, were emphasized more than HIV and family planning. Participants also reported a number of misconceptions about contraception, particularly around oral contraceptives and intrauterine devices, and STI transmission. Participants expressed the need to build trust in outreach workers and linkages, affirming the emphasis on the link within the Mobile Link project. Lastly, from the IDIs, FEWs living with HIV highlighted wanting supportive/messages to address depressive feelings that may stem from their perceived stigma. CONCLUSIONS: Utilizing participatory methodologies was demonstrated to be useful in intervention content creation and program implementation. As a result of this intervention development process, the research team gleaned lessons that may be applicable to future mHealth projects including the idea of adding some layers of choice to mHealth interventions for further tailoring at the individual level and the importance of human contact and trusting relationship.

Acceptability of active case finding with a seed-and-recruit model to improve tuberculosis case detection and linkage to treatment in Cambodia: A qualitative study.

BACKGROUND: With support of the national tuberculosis (TB) program, KHANA (a local non-governmental organization in Cambodia) has implemented an innovative approach using a seed-and-recruit model to actively find TB cases in the community. The model engaged community members including TB survivors as seed and newly diagnosed people with TB as recruiters to recruit presumptive TB cases in their social network in a snowball approach for screening and linkage to treatment. This study aimed to explore the acceptability of the active case finding with the seed-and-recruit model in detecting new TB cases and determine the characteristics of successful seeds. METHODS: This qualitative study was conducted in four provinces (Banteay Meanchey, Kampong Chhnang, Siem Reap, and Takeo) in Cambodia in 2017. Fifty-six in-depth interviews and ten focus group discussions (with a total of 64 participants) were conducted with selected beneficiaries and key stakeholders at different levels to gain insights into the acceptability, strengths, and challenges in implementing the model and the characteristics of successful seeds. Transcripts were coded and content analyses were performed. RESULTS: The seed-and-recruit active case finding model was generally well-received by the study participants. They saw the benefits of engaging TB survivors and utilizing their social network to find new TB cases in the community. The social embeddedness of the model within the local community was one of the major strengths. The success of the model also hinges on the integration with existing health facilities. Having an extensive social network, being motivated, and having good knowledge about TB were important characteristics of successful seeds. Study participants reported challenges in motivating the presumptive TB cases for screening, logistic capacities, and high workload during the implementation. However, there was a general consensus that the model ought to be expanded. CONCLUSIONS: These findings indicate that the seed-and-recruit model is well-accepted by the beneficiaries and key stakeholders. Further studies are needed to more comprehensively evaluate the impacts and cost-effectiveness of the model for future expansion in Cambodia as well as in other resource-limited settings.

Prevalence and correlates of HIV infection among people who use drugs in Cambodia: a cross-sectional survey using respondent driven sampling method.

BACKGROUND: Most of studies on the relationship between drug use and HIV have focused largely on people who inject drugs. Non-injecting drug use is much more common than injecting drug use, and although it can also predispose people to HIV infection, it is not widely explored. We therefore conducted this study to explore the prevalence of HIV and identify risk factors for HIV infection among people who use non-injecting drugs (PWUD) in Cambodia. METHODS: This cross-sectional study was conducted in 2017. The Respondent Driven Sampling method was used to recruit the study participants who were interviewed face-to-face using a structured questionnaire. Blood samples were collected for HIV and syphilis testing. A multivariable logistic regression analysis was conducted to identify risk factors associated with HIV infection. RESULTS: In total, 1367 PWUD were included in this study, whose mean age was 28.0 (SD = 7.7) years. The majority (95.1%) of the participants used methamphetamine. The prevalence of HIV was 5.7, and 35.2% of the identified HIV-positive PWUD were not aware of their status prior to the survey. After adjustment for other covariates, HIV infection remained significantly associated with being in the age group of ≥35 (AOR = 2.34, 95% CI = 1.04-6.11), having lower level of formal education of ≤ 6 years (AOR = 2.26, 95% CI = 1.04-5.15), living on the streets (AOR = 2.82, 95% CI = 1.10-7.23), perception that their HIV risk was higher as compared to that of the general population (AOR = 3.18, 95% CI = 1.27-8.62), having used injecting drugs in lifetime (AOR = 3.8, 95% CI = 1.36-4.56), and having cuts or sores around the genital area in the past 12 months (AOR = 3.42, 95% CI = 1.09-6.33). CONCLUSIONS: The prevalence of HIV among PWUD in this study was more than 10 times higher than the prevalence in the general adult population. The findings reveal a higher vulnerability to HIV infection among specific sub-populations of PWUD, such as those who are homeless, who may benefit from tailored interventions that respond to their specific needs. To enhance HIV case finding, stratification of PWUD to facilitate HIV risk profiling based on socio-economic profiles and drug injection history is recommended.

Characteristics of adolescents living with HIV receiving care and treatment services in antiretroviral therapy clinics in Cambodia: descriptive findings from a cross-sectional study.

BACKGROUND: Adolescents living with HIV experience worse HIV care outcomes compared to adults, especially during transition from pediatric to adult care. However, data regarding adolescents are limited. This paper describes and compares characteristics of male and female adolescents living with HIV preparing for transition from pediatric to adult care in Cambodia. METHODS: This cross-sectional study was conducted in August 2016 among 328 adolescents aged 15-17, randomly selected from 11 antiretroviral therapy (ART) clinics. Data were collected using a structured questionnaire, and descriptive analyses were conducted to compare characteristics of male and female adolescents. RESULTS: Of total, 55.2% were male, and 40.8% were living with parents. Majority (82.6%) got HIV infection from their mothers. Overall, adolescents had received ART for an average of 8.4 years, and HIV care for 9.5 years. Additionally, 82.4% were on first line ART regimen. Mean CD4 count from the most recent test was 672 cells/mm3, and viral load was 7686 copies/mL. Overall, 95.6% were adherent to ART on Visual Analogue Scale. About half (50.7%) had never disclosed their HIV status to anyone, while the remaining had disclosed it to their siblings (24.2%), friends (13.0%), schoolteachers (2.4%), or other (5.8%). A fifth reported having had boy or girlfriends, but few (2.1%) had ever had sexual intercourse. Females were more likely to have been engaged in sexual intercourse, and none reported having used a condom in their last intercourse. Few participants reported having ever used tobacco (1.8%), or any kind of illicit drugs (0.9%), but almost a fifth (20.7%) had a history of alcohol use. The majority (82.1%) were aware that they were receiving ART. HIV-related knowledge was suboptimal among the sample. CONCLUSIONS: This study provides a snapshot of immunological, virological, adherence, and disclosure outcomes that should be tracked during and following healthcare transition to evaluate the effectiveness of the transition program. Findings showed high ART adherence, low likelihood of disclosure outside of family circles, sub-optimal condom use, and poor knowledge of HIV. To provide individualized support for healthcare transition, pediatric and adult clinics need to ensure that these characteristics are taken into account.

Social and behavioural factors associated with risky sexual behaviours among university students in nine ASEAN countries: a multi-country cross-sectional study.

While university students are potential human resources, this population group is particularly involved in health risk behaviours. Preventing risky sexual behaviours among them would contribute to prevention of HIV, sexually transmitted infections (STIs), and unwanted pregnancies, which have posed a great burden on population health. This study was therefore conducted to identify social and behavioural factors associated with risky sexual behaviours among university students in nine ASEAN countries. A multi-country, cross-sectional study was conducted in 2015 among university students by a network of researchers in the selected countries. A convenient sampling method and stratified random sampling procedures were employed to select universities and students, respectively. A structured questionnaire was translated into national languages of the participating countries and used to collect data from the selected students in the classrooms. Using STATA, Chi-square test was used to test differences in proportions, and multinomial logistic regression analyses were performed to obtain relative risk ratios and 95% confidence intervals. Multivariate logistic regression analysis was performed with to identify independent social and behavioural factors associated with non-condom use at last sexual intercourse. In total, 8,836 students with a mean age of 20.6 (SD = 2.0) participated in the study. Most of them (98.5%) were unmarried. In all countries, male students were significantly more likely to have two or more sexual partners in the past 12 months compared to female students (4.8% vs. 1.1%, p < 0.001). Female students were significantly more likely to report unprotected sex compared to male students (50.5% vs. 58.8%, p = 0.01). Results of multivariable logistic regression analyses showed that students who reported having two or more partners in the past 12 months were significantly more likely to be male, be aged between 20-30, be current tobacco smokers, be binge drinkers, have severe depressive symptoms, and have been in a physical fight in the past 12 months, compared to students who reported having less than two sexual partners in the past 12 months. Health intervention programmes to prevent and control STIs, especially HIV infection, should focus on university students having the social and behavioural characteristics that are associated with risky sexual behaviours.

Sexual behaviors, HIV knowledge, HIV testing attitudes and recent HIV testing among female entertainment workers in Cambodia: A cross-sectional study.

BACKGROUND: In Cambodian context, female entertainment workers (FEWs) are young women working at establishments such as karaoke bars, restaurants, beer gardens or massage parlors. FEWs may sell sex to male patrons and are considered a high-risk group for HIV. This study aimed to identify factors associated with recent HIV testing among FEWs in Cambodia to inform future prevention activities. METHODS: Data were collected in 2014 as part of the evaluation of a larger HIV prevention project. A two-stage cluster sampling method was used to select participants from Phnom Penh and Siem Reap for face-to-face interviews using a structured questionnaire. A logistic regression model was constructed to identify independent factors associated with recent HIV testing. RESULTS: Data were collected from 667 FEWs with a mean age of 25.6 (SD = 5.5). Of total, 81.7% reported ever having had an HIV test, and 52.8% had at least one test in the past six months. After adjustment for other covariates, factors independently associated with recent HIV testing included living in Phnom Penh (AOR = 2.17, 95% CI = 1.43-3.28), having received HIV education in the past six months (AOR = 3.48, 95% CI = 2.35-5.15), disagreeing with a statement that 'I would rather not know if I have HIV' (AOR = 2.15, 95% CI = 1.41-3.30), agreeing with a statement that 'getting tested for HIV helps people feel better' (AOR = 0.32, 95% CI = 0.13-0.81) and not using a condom in the last sexual intercourse with a non-commercial partner (AOR = 0.48, 95% CI = 0.26-0.88). CONCLUSIONS: FEWs with greater knowledge and positive attitudes towards HIV testing got tested for HIV more frequently than those with lesser knowledge and less positive attitudes. These findings suggest that future interventions should focus on disseminating tailored health messages around testing practices as well as specific topics such as condom use with non-commercial partners.

Patterns of HIV testing, drug use, and sexual behaviors in people who use drugs: findings from a community-based outreach program in Phnom Penh, Cambodia.

BACKGROUND: People who use drugs are an important priority for HIV programs. However, data related to their utilization of HIV services are limited. This paper reports patterns of HIV testing, drug use, and risk and service perception among people who use drugs. Study participants were receiving HIV and harm reduction services from a community-based program in Phnom Penh, comprised of itinerant peer-led outreach and static drop-in centers. METHODS: This was a mixed-methods study conducted in 2014, comprising of a quantitative survey using a structured questionnaire, followed by two focus group discussions among a sub-sample of survey participants. Participants were recruited from hotspots in five HIV high-burden communes using a two-stage cluster sampling method. Quantitative descriptive analyses and qualitative thematic analyses were performed. RESULTS: This study included 151 people who use drugs with a mean age of 31.2 (SD = 6.5) years; 77.5% were male and 39.1% were married. The most common drugs used were methamphetamines (72.8%) and heroin (39.7%), and 38.0% injected drugs in the past 3 months. Overall, 83.3% had been tested for HIV in the past 6 months, of whom 62.5% had been tested by peers through community-based outreach. However, there were ongoing HIV risks: 37.3% were engaging in sex on drugs, only 35.6% used a condom at last sexual intercourse, and 10.8% had had a sexually transmitted infection in the last 6 months. Among people who reported injecting drugs in the past 3 months, 27.5% reported re-using needles/syringes. Almost half (46.5%) perceived themselves as being at lower risk of HIV compared to the general population. Qualitative results contextualized the findings of low perception of HIV risks and suggested that although services were often unavailable on weekends, at night, or during national holidays, peer-led community-based outreach was highly accepted. CONCLUSIONS: A peer-led community-based approach was effective in reaching people who use drugs with HIV and harm reduction interventions. To mitigate ongoing HIV risks, expanding access to combination prevention interventions and implementing strategies to enable people who use drugs to objectively assess their HIV risks are required. Additionally, community-based programs should collect data along the care continuum, to enable decentralized tracking of progress towards 90-90-90 goals at local levels.

Using risk-tracing snowball approach to increase HIV case detection among high-risk populations in Cambodia: an intervention study.

BACKGROUND: Early HIV diagnosis and initiation onto antiretroviral therapy may prevent ongoing spread of HIV. Risk Tracing Snowball Approach (RTSA) has been shown to be effective in detecting new HIV cases in other settings. The main objective of this study is to evaluate the effectiveness of RTSA in increasing the rate of newly identified HIV cases among high-risk populations. Our second objective was to evaluate the effectiveness of RTSA, as compared to the walk-in group, in increasing the number of HIV tests and early case detection. METHODS: This study was conducted from April 1 to September 30, 2016 at two NGO clinics in Phnom Penh, Cambodia. Respondent driven sampling method was adapted to develop RTSA to reach high-risk populations, including key populations and the general population who have social connections with key populations. Bivariate and multivariate logistic regression analyses were conducted. RESULTS: During the implementation period, 721 clients walked in for HIV testing (walk-in group), and all were invited to be seeds. Of the invited clients, 36.6% agreed to serve as seeds. Throughout the implementation, 6195 coupons were distributed to seeds or recruiters, and resulted in 1572 clients visiting the two clinics with coupons (RTSA group), for a coupon return rate of 25.3%. The rate of newly identified HIV cases among the RTSA group was significantly lower compared to that in walk-in group. However, the highest number of newly identified HIV cases was found during the implementation period, compared to both pre- and post-implementation period. Although statistically not significant, the mean CD4 count of newly identified HIV cases detected through RTSA was almost 200 cells/mm3 higher than that in the walk-in group. CONCLUSIONS: Although the rate of newly identified HIV cases among the RTSA group was lower than that in the walk-in group, the inclusion of RTSA in addition to the traditional walk-in method boosted new HIV case detection in the two participating clinics. A higher mean CD4 count for the RTSA group may reveal that RTSA may be able to detect HIV cases earlier than the traditional walk-in approach. Further research is needed to understand whether RTSA is a cost-effective intervention to prevent ongoing spread of the HIV among high-risk populations in Cambodia.