An International Legal Framework to Address Antimicrobial Resistance

Antimicrobial resistance is a growing threat to global health. Currently it accounts for approximately 700,000 deaths annually, but is predicted to cause as many as 10,000,000 deaths by 2050 if nothing is done to address it. To effectively deal with this problem three areas must be addressed simultaneously: access, conservation, and innovation. However, solving issues of access, conservation and innovation at the same time requires new coordination and financing mechanisms, some of which must be organized globally. This bulletin outlines the possible role that a binding international legal framework can play in the fight against antimicrobial resistance

Water dispersible microbicidal cellulose acetate phthalate film

BACKGROUND: Cellulose acetate phthalate (CAP) has been used for several decades in the pharmaceutical industry for enteric film coating of oral tablets and capsules. Micronized CAP, available commercially as "Aquateric" and containing additional ingredients required for micronization, used for tablet coating from water dispersions, was shown to adsorb and inactivate the human immunodeficiency virus (HIV-1), herpesviruses (HSV) and other sexually transmitted disease (STD) pathogens. Earlier studies indicate that a gel formulation of micronized CAP has a potential as a topical microbicide for prevention of STDs including the acquired immunodeficiency syndrome (AIDS). The objective of endeavors described here was to develop a water dispersible CAP film amenable to inexpensive industrial mass production. METHODS: CAP and hydroxypropyl cellulose (HPC) were dissolved in different organic solvent mixtures, poured into dishes, and the solvents evaporated. Graded quantities of a resulting selected film were mixed for 5 min at 37°C with HIV-1, HSV and other STD pathogens, respectively. Residual infectivity of the treated viruses and bacteria was determined. RESULTS: The prerequisites for producing CAP films which are soft, flexible and dispersible in water, resulting in smooth gels, are combining CAP with HPC (other cellulose derivatives are unsuitable), and casting from organic solvent mixtures containing ≈50 to ≈65% ethanol (EtOH). The films are ≈100 µ thick and have a textured surface with alternating protrusions and depressions revealed by scanning electron microscopy. The films, before complete conversion into a gel, rapidly inactivated HIV-1 and HSV and reduced the infectivity of non-viral STD pathogens >1,000-fold. CONCLUSIONS: Soft pliable CAP-HPC composite films can be generated by casting from organic solvent mixtures containing EtOH. The films rapidly reduce the infectivity of several STD pathogens, including HIV-1. They are converted into gels and thus do not have to be removed following application and use. In addition to their potential as topical microbicides, the films have promise for mucosal delivery of pharmaceuticals other than CAP

Effects of Genital Ulcer Disease and Herpes Simplex Virus Type 2 on the Efficacy of Male Circumcision for HIV Prevention: Analyses from the Rakai Trials

Ron Gray and colleagues analyze data from two circumcision trials in Uganda to assess how HSV-2 status and genital ulcer disease affect the procedure's ability to reduce HIV infection

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721

HIV and Syphilis Co-Infection Increasing among Men Who Have Sex with Men in China: A Systematic Review and Meta-Analysis

BACKGROUND: This study aims to estimate the magnitude and changing trends of HIV, syphilis and HIV-syphilis co-infections among men who have sex with men (MSM) in China during 2003-2008 through a systematic review of published literature. METHODOLOGY/PRINCIPAL FINDINGS: Chinese and English literatures were searched for studies reporting HIV and syphilis prevalence among MSM from 2003 to 2008. The prevalence estimates were summarized and analysed by meta-analyses. Meta-regression was used to identify the potential factors that are associated with high heterogeneities in meta-analysis. Seventy-one eligible articles were selected in this review (17 in English and 54 in Chinese). Nationally, HIV prevalence among MSM increased from 1.3% during 2003-2004 to 2.4% during 2005-2006 and to 4.7% during 2007-2008. Syphilis prevalence increased from 6.8% during 2003-2004 to 10.4% during 2005-2006 and to 13.5% during 2007-2008. HIV-syphilis co-infection increased from 1.4% during 2005-2006 to 2.7% during 2007-2008. Study locations and study period are the two major contributors of heterogeneities of both HIV and syphilis prevalence among Chinese MSM. CONCLUSIONS/SIGNIFICANCE: There have been significant increases in HIV and syphilis prevalence among MSM in China. Scale-up of HIV and syphilis screening and implementation of effective public health intervention programs should target MSM to prevent further spread of HIV and syphilis infection

Using European travellers as an early alert to detect emerging pathogens in countries with limited laboratory resources

BACKGROUND: The volume, extent and speed of travel have dramatically increased in the past decades, providing the potential for an infectious disease to spread through the transportation network. By collecting information on the suspected place of infection, existing surveillance systems in industrialized countries may provide timely information for areas of the world without adequate surveillance currently in place. We present the results of a case study using reported cases of Shigella dysenteriae serotype 1 (Sd1) in European travellers to detect "events" of Sd1, related to either epidemic cases or endemic cases in developing countries. METHODS: We identified papers from a Medline search for reported events of Sd1 from 1940 to 2002. We requested data on shigella infections reported to the responsible surveillance entities in 17 European countries. Reports of Sd1 from the published literature were then compared with Sd1 notified cases among European travellers from 1990 to 2002. RESULTS: Prior to a large epidemic in 1999–2000, no cases of Sd1 had been identified in West Africa. However, if travellers had been used as an early warning, Sd1 could have been identified in this region as earlier as 1992. CONCLUSION: This project demonstrates that tracking diseases in European travellers could be used to detect emerging disease in developing countries. This approach should be further tested with a view to the continuous improvement of national health surveillance systems and existing European networks, and may play a significant role in aiding the international public health community to improve infectious disease control

Modelling the impact and cost-effectiveness of the HIV intervention programme amongst commercial sex workers in Ahmedabad, Gujarat, India.

BACKGROUND: Ahmedabad is an industrial city in Gujarat, India. In 2003, the HIV prevalence among commercial sex workers (CSWs) in Ahmedabad reached 13.0%. In response, the Jyoti Sangh HIV prevention programme for CSWs was initiated, which involves outreach, peer education, condom distribution, and free STD clinics. Two surveys were performed among CSWs in 1999 and 2003. This study estimates the cost-effectiveness of the Jyoti Sangh HIV prevention programme. METHODS: A dynamic mathematical model was used with survey and intervention-specific data from Ahmedabad to estimate the HIV impact of the Jyoti Sangh project for the 51 months between the two CSW surveys. Uncertainty analysis was used to obtain different model fits to the HIV/STI epidemiological data, producing a range for the HIV impact of the project. Financial and economic costs of the intervention were estimated from the providers perspective for the same time period. The cost per HIV-infection averted was estimated. RESULTS: Over 51 months, projections suggest that the intervention averted 624 and 5,131 HIV cases among the CSWs and their clients, respectively. This equates to a 54% and 51% decrease in the HIV infections that would have occurred among the CSWs and clients without the intervention. In the absence of intervention, the model predicts that the HIV prevalence amongst the CSWs in 2003 would have been 26%, almost twice that with the intervention. Cost per HIV infection averted, excluding and including peer educator economic costs, was USD 59 and USD 98 respectively. CONCLUSION: This study demonstrated that targeted CSW interventions in India can be cost-effective, and highlights the importance of replicating this effort in other similar settings.Published versio

C. albicans Colonization of Human Mucosal Surfaces

Background: Candida albicans is a low level commensal organism in normal human populations with the continuous potential to expand and cause a spectrum of clinical conditions. Methodology/Principal Findings: Using ex vivo human organ cultures and populations of primary human cells, we have developed several related experimental systems to examine early-stage interactions between C. albicans and mucosal surfaces. Experiments have been conducted both with exogenously added C. albicans and with overtly normal human mucosal surfaces supporting pre-existing infections with natural isolates of Candida. Under different culture conditions, we have demonstrated the formation of C. albicans colonies on human target cells and filament formation, equivalent to tissue invasion. Conclusions/Significance: These organ culture systems provide a valuable new resource to examine the molecular and cellular basis for Candida colonization of human mucosal surfaces

Deliverable 3.6 zoning plan of case studies : evaluation of spatial management options for the case studies

Within MESMA, nine case studies (CS) represent discrete marine European spatial entities, at different spatial scales, where a spatial marine management framework is in place, under development or considered. These CS (described in more details below) are chosen in such a way (MESMA D. 3.1 ) that they encompass the complexity of accommodating the various user functions of the marine landscape in various regions of the European marine waters. While human activities at sea are competing for space, there is also growing awareness of the possible negative effects of these human activities on the marine ecosystem. As such, system specific management options are required, satisfying current and future sectoral needs, while safeguarding the marine ecosystem from further detoriation. This integrated management approach is embedded in the concept of ecosystem based management (EBM). The goal of marine EBM is to maintain marine ecosystems in a healthy, productive and resilient condition, making it possible that they sustain human use and provide the goods and services required by society (McLeod et al. 2005). Therefore EBM is an environmental mangagement approach that recognises the interactions within a marine ecosystem, including humans. Hence, EBM does not consider single issues, species or ecosystems good and services in isolation. Operationalisation of EBM can be done through place-based or spatial management approaches (Lackey 1998), such as marine spatial planning (MSP). MSP is a public process of analysing and allocating the spatial and temporal distribution of human activities aiming at achieving ecological, economic and social objectives. These objectives are usually formulated through political processes (Douvere et al. 2007, Douvere 2008). Within MESMA, a spatially managed area (SMA) is then defined as “a geographical area within which marine spatial planning initiatives exist in the real world”. Marine spatial planning initiatives refer to existing management measures actually in place within a defined area, or in any stage of a process of putting management in place, e.g. plans or recommendations for a particular area. Management can include management for marine protection (e.g. in MPAs), or management for sectoral objectives (e.g. building a wind farm to meet renewable energy objectives). Within MESMA, SMAs can have different spatial scales. A SMA can be a small, specific area that is managed/planned to be managed for one specific purpose, but it can also be a larger area within which lots of plans or ‘usage zones’ exist. This definition is different from the definition mentioned in the DoW (page 60). The original definition was adapted during a CS leader workshop (2-4 May 2012 in Gent, Belgium) and formally accepted by the MESMA ExB during the ExB meeting in Cork (29-30 May 2012). MSP should result in a marine spatial management plan that will produce the desired future trough explicit decisions about the location and timing of human activities. Ehler & Douvere (2009) consider this spatial management as a beginning toward the the implementation of desired goals and objectives. They describe the spatial management plan as a comprehensive, strategic document that provides the framework and direction for marine spatial management decisions. The plan should identify when, where and how goals and objectives will be met. Zoning (the development of zoning plans) is often an important management measure to implement spatial management plans. The purpose of a zoning plan (Ehler & Douvere 2009) is: To provide protection for biologically and ecologically important habitats, ecosystems, and ecological processes. To seperate conflicting human activities, or to combine compatible activities. To protect the natural values of the marine management area (in MESMA terminology: the SMA) while allowing reasonable human uses of the area. To allocate areas for reasonable human uses while minimising the effects of these human uses on each other, and nature. To preserve some areas of the SMA in their natural state undisturbed by humans except for scientific and educational purposes.peer-reviewe

The Prevalence of Sexually Transmitted Infections in Papua New Guinea: A Systematic Review and Meta-Analysis

Patellofemoral osteoarthritis (PF OA) is more prevalent than previously thought and contributes to patient's suffering from knee OA. Synthesis of prevalence data can provide estimates of the burden of PF OA