Toxoplasma gondii merozoite gene expression analysis with comparison to the life cycle discloses a unique expression state during enteric development

BACKGROUND: Considerable work has been carried out to understand the biology of tachyzoites and bradyzoites of Toxoplasma gondii in large part due to in vitro culture methods for these stages. However, culturing methods for stages that normally develop in the gut of the definitive felid host, including the merozoite and sexual stages, have not been developed hindering the ability to study a large portion of the parasite’s life cycle. Here, we begin to unravel the molecular aspects of enteric stages by providing new data on merozoite stage gene expression. RESULTS: To profile gene expression differences in enteric stages we harvested merozoites from the intestine of infected cats and hybridized mRNA to the Affymetrix Toxoplasma GeneChip. We analyzed the merozoite data in context of the life cycle by comparing it to previously published data for the oocyst, tachyzoite, and bradyzoite stages. Principal component analysis highlighted the unique profile of merozoites, placing them approximately half-way on a continuum between the tachyzoite/bradyzoite and oocyst samples. Prior studies have shown that antibodies to surface antigen one (SAG1) and many dense granule proteins do not label merozoites: our microarray data confirms that these genes were not expressed at this stage. Also, the expression for many rhoptry and microneme proteins was drastically reduced while the expression for many surface antigens was increased at the merozoite stage. Gene Ontology and KEGG analysis revealed that genes involved in transcription/translation and many metabolic pathways were upregulated at the merozoite stage, highlighting unique growth requirements of this stage. To functionally test these predictions, we demonstrated that an upstream promoter region of a merozoite specific gene was sufficient to control expression in merozoites in vivo. CONCLUSIONS: Merozoites are the first developmental stage in the coccidian cycle that takes place within the gut of the definitive host. The data presented here describe the global gene expression profile of the merozoite stage and the creation of transgenic parasite strains that show stage-specific expression of reporter genes in the cat intestine. These data and reagents will be useful in unlocking how the parasite senses and responds to the felid gut environment to initiate enteric development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-350) contains supplementary material, which is available to authorized users

Social innovation in sexual health: a scoping review towards ending the HIV epidemic.

As donor financial support decreases, ending the HIV epidemic in Asia will require novel and sustainable approaches. Social innovation, a community-engaged process that links social change and health improvement, may be useful for helping to end the HIV epidemic in Asia. A scoping review to examine social innovation strategies in sexual health for the Asian region was conducted. The research identified focused on three types of social innovation: (1) microfinance; (2) social entrepreneurship; and (3) social enterprise. Microfinance provides financial opportunities (e.g. banking services, job opportunities) to spur local entrepreneurship and healthier behaviours. Social entrepreneurship uses business principles and tools (e.g. crowdsourcing, human-centred design) to improve health. Social enterprise is a business with a social mission. Further research is needed to measure the efficacy and cost-effectiveness of social innovation strategies in improving HIV services

Blocking and being blocked on gay dating apps among MSM attending a sexual health clinic: an observational study

Background There are limited studies on blocking and men who have sex with men (MSM) health outcomes. We need such data in China, to better understand the relationship between Chinese MSM gay app use and health outcomes, thus providing insight on risky sexual behaviors and HIV transmission among Chinese MSM - one of the world's largest MSM communities. Blocking someone is when users select a function on an app to prevent another user from contacting them and being blocked is when someone is prevented from contacting another user. We studied the correlates of blocking on the world's largest gay dating app among Chinese MSM (N = 208). Methods We conducted a cross-sectional survey as part of an HIV testing intervention in Guangzhou, China, May-December 2019. Using logistic regression models, we estimated the correlates of blocking (e.g. sociodemographic characteristics, sexual behavior, HIV testing history, social network data). Results MSM had a mean age of 27.9 years (SD = 7.1) and median of one sexual partner in the last 3 months. About 62% had blocked someone in their lifetime and 46% had been blocked in their lifetime. Each additional male partner was associated with an 87% (aOR = 1.87, 95%CI = 1.03, 3.40) increased chance of being blocked. Reporting a versatile sexual role was related with a 90% (aOR = 0.10, 95%CI = 0.02, 0.45) decreased likelihood of blocking behavior and an 86% (aOR = 0.14, 95%CI = 0.04, 0.46) reduced chance of being blocked. Conclusions Number of male partners may be associated with blocking behavior, with implications for the design of online sexual health interventions

Pay-it-forward gonorrhea and chlamydia testing among men who have sex with men in China:a study protocol for a three-arm cluster randomized controlled trial

BACKGROUND: Gonorrhea and chlamydia testing rates are poor among Chinese men who have sex with men (MSM). A quasi-experimental study suggested that a pay-it-forward strategy increased dual gonorrhea/chlamydia testing among MSM. Pay-it-forward offers an individual a gift (e.g., a free test) and then asks the same person if they would like to give a gift to another person. This article reports the protocol of a randomized controlled trial to evaluate dual gonorrhea/chlamydia test uptake and other outcomes among MSM in three arms - a pay-it-forward arm, a pay-what-you-want arm, and a standard of care arm. METHODS: Three hundred MSM will be recruited at three HIV testing sites in Guangzhou and Beijing. Testing sites include two hospital-based MSM sexually transmitted diseases clinics and one MSM community-based organization. Eligible participants will be born biologically male, aged 16 years or older, reporting previous anal sex with another man, having never participated in the pay-it-forward program, without previous gonorrhea and chlamydia testing in the past 12 months, and residing in China. Following a cluster randomized design, every cluster of ten participants will be randomly allocated into one of three arms: (1) a pay-it-forward arm in which men are offered free gonorrhea and chlamydia testing and then asked whether they would like to donate ("pay it forward") toward testing for future testers; (2) a pay-what-you-want arm in which men are offered free testing and told to decide how much to pay after receiving the test; (3) a standard of care arm in which men can pay the full price for dual gonorrhoea and chlamydia testing. The primary outcome is dual gonorrhoea/chlamydia testing as verified by administrative records. Secondary outcomes include incremental cost per test, incremental cost per diagnosis, community connectedness, and social cohesion. Primary outcome will be calculated for each arm using intention-to-treat and compared using one-sided 95% confidence intervals with a margin of 20% increase defined as superiority. DISCUSSION: This study will examine the pay-it-forward strategy in comparison to the standard of care in improving test uptake for gonorrhea and chlamydia. We will leverage the cluster randomized controlled trial to provide scientific evidence on the potential effect of pay-it-forward. Findings from this study will shed light on novel intervention methods for increasing preventive health service utilization and innovate ways to finance it among communities. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03741725 . Registered on 12 November 2018

Pay-it-forward gonorrhoea and chlamydia testing among men who have sex with men in China:a randomised controlled trial

BACKGROUND: WHO recommends that men who have sex with men (MSM) receive gonorrhoea and chlamydia testing, but many evidence-based preventive services are unaffordable. The pay-it-forward strategy offers an individual a gift (eg, a test for sexually transmitted diseases) and then asks whether they would like to give a gift (eg, a future test) to another person. This study examined the effectiveness of a pay-it-forward programme to increase gonorrhoea and chlamydia testing among MSM in China. METHODS: We did a randomised controlled superiority trial at three HIV testing sites run by MSM community-based organisations in Guangzhou and Beijing, China. We included MSM aged 16 years or older who were seeking HIV testing and met indications for gonorrhoea and chlamydia testing. Restricted randomisation was done using computer-generated permuted blocks. 30 groups were randomised into three arms (1:1:1): a pay-it-forward arm in which men were offered free gonorrhoea and chlamydia testing and then asked whether they would like to donate for testing of prospective participants, a pay-what-you-want arm in which men were offered free testing and given the option to pay any desired amount for the test, and a standard-of-care arm in which testing was offered at ¥150 (US$22). There was no masking to arm assignment. The primary outcome was gonorrhoea and chlamydia test uptake ascertained by administrative records. We used generalised estimating equations to estimate intervention effects with one-sided 95% CIs and a prespecified superiority margin of 20%. The trial is registered with ClinicalTrials.gov, NCT03741725. FINDINGS: Between Dec 8, 2018, and Jan 19, 2019, 301 men were recruited and included in the analysis. 101 were randomly assigned to the pay-it-forward group, 100 to the pay-what-you-want group, and 100 to the standard-of-care group. Test uptake for gonorrhoea and chlamydia was 56% (57 of 101 participants) in the pay-it-forward arm, 46% (46 of 100 participants) in the pay-what-you-want arm, and 18% (18 of 100 participants) in the standard-of-care arm. The estimated difference in test uptake between the pay-it-forward and standard-of-care group was 38·4% (95% CI lower bound 28·4%). Among men in the pay-it-forward arm, 54 of 57 (95%) chose to donate to support testing for others. INTERPRETATION: The pay-it-forward strategy can increase gonorrhoea and chlamydia testing uptake among Chinese MSM and could be a useful tool for scaling up preventive services that carry a mandatory fee. FUNDING: US National Institute of Health; Special Programme for Research and Training in Tropical Diseases, sponsored by UNICEF, UNDP, World Bank, and WHO; the National Key Research and Development Program of China; Doris Duke Charitable Foundation; and Social Entrepreneurship to Spur Health

Leading by Example: Web-Based Sexual Health Influencers Among Men Who Have Sex With Men Have Higher HIV and Syphilis Testing Rates in China

BACKGROUND: The spread of healthy behaviors through social networks may be accelerated by influential individuals. Previous studies have used lay health influencers to prevent sexually transmitted infections (STIs) among internet-using men who have sex with men (MSM). However, there is a lack of understanding of the characteristics of this key subset of MSM. OBJECTIVE: This study aimed to examine sociodemographic characteristics, HIV and syphilis testing, and sexual behaviors of Web-based MSM sexual health influencers (SHIs) in China, defined as individuals with relatively stronger influence on spreading HIV and STI information online. METHODS: A Web-based survey of MSM was conducted in August 2017 as a final follow-up of a randomized controlled trial promoting HIV testing in 8 Chinese cities. Men were recruited through a gay social networking mobile phone app and were included if they were born biologically male, aged 16 years and above, ever had sex with another man, and HIV negative or with unknown HIV status. Information regarding sociodemographic characteristics, sexual behaviors, and HIV and syphilis testing was obtained. We assessed men's Web-based sexual health influence using a standardized 6-item opinion leadership scale focused on HIV and STI information. Influencers were defined as those whose mean score ranked within the top 13% (a higher score means greater influence). We used multivariable linear and logistic regression models to measure Web-based sexual health influence's association with HIV and syphilis testing, controlling for intervention trial effects, age, education, income, and marital status. RESULTS: Overall, 1031 men completed the survey. Most men were younger than 30 years (819/1031, 79.43%) and had at least college education (667/1031, 64.69%). Influencers were more likely to get tested for HIV (73/132, 55.3% vs 337/899, 37.5%; P<.001) and syphilis (35/132, 26.5% vs 137/899, 15.2%; P=.001) in the last 3 months compared with noninfluencers. There were no significant differences in condomless sex with male partners (26/132, 19.7% vs 203/899, 22.6%; P=.46), mean number of male sex partners (1.32 vs 1.11; P=.16) in the last 3 months, and mainly meeting male sex partners online in the last 12 months (97/132, 73.5% vs 669/899, 74.4%; P=.82) between influencers and noninfluencers. Regression analyses showed that influencers had higher odds of HIV testing (adjusted odds ratio, AOR 2.16, 95% CI 1.48-3.17) and syphilis testing (AOR 1.99, 95% CI 1.28-3.10) in the last 3 months. CONCLUSIONS: We identified Web-based SHIs who might be more likely to help promote healthy HIV and syphilis testing behaviors through MSM populations. Leveraging existing influencers may help improve HIV and syphilis testing among their networks

Community engagement in sexual health and uptake of HIV testing and syphilis testing among MSM in China: a cross-sectional online survey.

INTRODUCTION: HIV and syphilis testing rates remain low among men who have sex with men (MSM) in low- and middle-income countries (LMICs). Community engagement has been increasingly used to promote HIV testing among key populations in high-income countries, often in settings with stronger civil society. This study aimed to assess socio-demographic, behavioural, and community engagement factors associated with HIV and syphilis testing among MSM in China. METHODS: MSM ≥16 years old who had condomless sex in the past three months were recruited nationwide to complete a cross-sectional online survey in November 2015. Data were collected on socio-demographics, sexual behaviours, HIV testing, syphilis testing, and community engagement in sexual health. We defined community engagement in sexual health using six items assessing awareness and advocacy of sexual health programmes. The underlying factor structure of a 6-item community engagement scale was determined through exploratory factor analysis. Univariate and multivariable logistic regressions identified correlates of HIV and syphilis testing. RESULTS: 1189 MSM were recruited. 54% (647/1189) of men had ever tested for HIV and 30% (354/1189) had ever tested for syphilis. Factor analysis suggested three levels of community engagement (minimal, moderate, and substantial) and this model explained 79.5% of observed variance. A quarter (26%, 312/1189) reported none to minimal engagement, over one half (54%, 644/1189) reported moderate engagement, and a fifth (20%, 233/1189) reported substantial engagement. Multivariable logistic regression showed that MSM with greater community engagement in sexual health were more likely to have ever tested for HIV (substantial vs. no engagement: aOR 7.91, 95% CI 4.98-12.57) and for syphilis (substantial vs. no engagement: aOR 5.35, 95% CI 3.16-9.04). CONCLUSION: HIV and syphilis testing are suboptimal among MSM in China. Community engagement may be useful for promoting testing in China and should be considered in intervention development and delivery. Further research is needed to better understand the role of LMIC community engagement in HIV interventions

Genomic analysis of a large set of currently—and historically—important human adenovirus pathogens

Human adenoviruses (HAdVs) are uniquely important “model organisms” as they have been used to elucidate fundamental biological processes, are recognized as complex pathogens, and are used as remedies for human health. As pathogens, HAdVs may effect asymptomatic or mild and severe symptomatic disease upon their infection of respiratory, ocular, gastrointestinal, and genitourinary systems. High-resolution genomic data have enhanced the understanding of HAdV epidemiology, with recombination recognized as an important and major pathway in the molecular evolution and genesis of emergent HAdV pathogens. To support this view and to actualize an algorithm for identifying, characterizing, and typing novel HAdVs, we determined the DNA sequence of 95 isolates from archives containing historically important pathogens and collections housing currently circulating strains to be sequenced. Of the 85 samples that were completely sequenced, 18 novel recombinants within species HAdV-B and D were identified. Two HAdV-D genomes were found to contain novel penton base and fiber genes with significant divergence from known molecular types. In this data set, we found additional isolates of HAdV-D53 and HAdV-D58, two novel genotypes recognized recently using genomics. This supports the thesis that novel HAdV genotypes are not limited to “one-time” appearances of the prototype but are of importance in HAdV epidemiology. These data underscore the significance of lateral genomic transfer in HAdV evolution and reinforce the potential public health impact of novel genotypes of HAdVs emerging in the population