Natural polyphenols: potential in the prevention of sexually transmitted viral infections.

Sexually transmitted viral infections represent a major public health concern due to lack of effective prevention strategies. Efforts are ongoing to develop modalities that can enable simultaneous prevention of multiple sexually transmitted infections. In the present review, we discuss the potential of natural polyphenols to prevent sexually transmitted viral infections. The review gives an account of various in vitro and in vivo studies carried out on epigallocatechin gallate, theaflavins (black tea polyphenols), resveratrol, genistein and curcumin to highlight their potential to prevent sexually transmitted infections caused by HIV (human immunodeficiency virus), HSV (herpes simplex virus) and HPV (human papilloma virus).

Safe male circumcision in Botswana: tension between traditional practices and biomedical marketing.

Botswana has been running Safe Male Circumcision (SMC) since 2009 and has not yet met its target. Donors like the US Centers for Disease Control and Prevention and Africa Comprehensive HIV/AIDS Partnership (funded by the Gates Foundation) in collaboration with Botswana's Ministry of Health have invested much to encourage HIV-negative men to circumcise. Demand creation strategies make use of media and celebrities. The objective of this paper is to explore responses to SMC in relation to circumcision as part of traditional initiation practices. More specifically, we present the views of two communities in Botswana on SMC consultation processes, implementation procedures and campaign strategies. The methods used include participant observation, in-depth interviews with key stakeholders (donors, implementers and Ministry officials), community leaders and men in the community. We observe that consultation with traditional leaders was done in a seemingly superficial, non-participatory manner. While SMC implementers reported pressure to deliver numbers to the World Health Organization, traditional leaders promoted circumcision through their routine traditional initiation ceremonies at breaks of two-year intervals. There were conflicting views on public SMC demand creation campaigns in relation to the traditional secrecy of circumcision. In conclusion, initial cooperation of local chiefs and elders turned into resistance.

Unpacking the 'structural' in a structural approach for HIV prevention among female sex workers: a case study from China.

Interventions for HIV prevention among female sex workers (FSWs) in China focus on HIV/sexually transmitted infection (STI) and individual behaviour change. An occupational health framework facilitates intervention across an array of health issues FSWs face including HIV/STI, violence, reproductive health, stigma and substance use. Through a case study of a community-based Jiaozhou (JZ) FSW programme, we developed a conceptual framework incorporating global discussions of structural approaches to HIV prevention with the specific social and structural contexts identified among FSWs in China. Based on ethnographic fieldwork between August 2010 and May 2013, we describe the evolution of this programme to its current occupational health focus and unpack the intervention strategies. We describe the critical features of the programme that have fostered success among FSWs including high-quality clinical services provided within a welcoming setting, responsive outreach work through staff and trained FSW peers, interpersonal and community-level engagement aimed at changing the local social and structural environments of sex work and tailored health education materials. This intervention differs from other projects in China by adopting a more holistic approach to FSW health that incorporates social issues. It also demonstrates the feasibility of structural interventions among FSWs even within an environment that has strong anti-prostitution policies.

Preclinical assessments of vaginal microbicide candidate safety and efficacy.

Sexually transmitted infections like HIV, HPV, and HSV-2, as well as unplanned pregnancy, take a huge toll on women worldwide. Woman-initiated multipurpose prevention technologies that contain antiviral/antibacterial drugs (microbicides) and a contraceptive to simultaneously target sexually transmitted infections and unplanned pregnancy are being developed to reduce these burdens. This review will consider products that are applied topically to the vagina. Rectally administered topical microbicides in development for receptive anal intercourse are outside the scope of this review. Microbicide and microbicide/contraceptive candidates must be rigorously evaluated in preclinical models of safety and efficacy to ensure that only candidates with favorable risk benefit ratios are advanced into human clinical trials. This review describes the comprehensive set of in vitro, ex vivo, and in vivo models used to evaluate the preclinical safety and antiviral efficacy of microbicide and microbicide/contraceptive candidates.

[Microbicides for preventing sexually transmitted infections: Current status and strategies for preclinical evaluation of new candidates]. / Microbicidas para la prevención de infecciones de transmisión sexual: estado actual y estrategias para la evaluación preclínica de nuevos candidatos.

Microbicides are a new tool, still under investigation, which could help prevent infection by the human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). Increasing evidence shows that the complexity of sexual transmission of viral pathogens requires the identification of compounds able to block the early events during the cycle of viral infection. In this manuscript we provide a comprehensive review of the different microbicide strategies that have been studied or are currently being considered for STI prevention, particularly emphasizing those having the potential to block HIV infection. The manuscript also reviews the complex process that is required to conduct future clinical studies in humans and concludes with a brief discussion of the strategies that could be part of the immediate future in microbicide research.

Microbicidas para la prevención de infecciones de transmisión sexual: estado actual y estrategias para la evaluación preclínica de nuevos candidatos. / [Microbicides for preventing sexually transmitted infections: Current status and strategies for preclinical evaluation of new candidates].

Microbicides are a new tool, still under investigation, which could help prevent infection by the human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). Increasing evidence shows that the complexity of sexual transmission of viral pathogens requires the identification of compounds able to block the early events during the cycle of viral infection. In this manuscript we provide a comprehensive review of the different microbicide strategies that have been studied or are currently being considered for STI prevention, particularly emphasizing those having the potential to block HIV infection. The manuscript also reviews the complex process that is required to conduct future clinical studies in humans and concludes with a brief discussion of the strategies that could be part of the immediate future in microbicide research.

Incidence of genital warts in adolescents and young adults in an integrated health care delivery system in the United States before human papillomavirus vaccine recommendations.

BACKGROUND: Information on genital wart incidence in adolescents and young adults before human papillomavirus (HPV) vaccination is important for understanding the impact of the vaccine on the epidemiology of this early outcome of HPV infection. METHODS: The study population included 11- to 29-year-old enrollees of Northern California Kaiser Permanente between July 1, 2000, and July 1, 2005, before the availability of the HPV vaccine. We identified genital warts with an algorithm combining genital wart-specific International Classification of Diseases, Ninth Revision, Clinical Modification codes (078.10, 078.11, and 078.19) with physician-recorded anatomic locations. We calculated sex- and age-specific incidence rates of genital warts and described the specific anatomic location of presentation, as well as recurrences of genital warts. RESULTS: We identified 1,682 cases of genital warts among 181,264 individuals. The incidence rate was highest among women (6.3/1000 person-years) and men (2.9/1000 person-years) aged 20 to 24 years old. Among women (n = 96,792), 63.4% of the 1240 incident genital wart cases occurred on the vulva and 21.1% on the cervix. Among men (n = 84,472), 91.6% of the 442 incident genital wart cases did not have a specific anatomic location recorded. Most people with an incident genital wart diagnosis (87.2%) did not have a recurrence during the observation period. CONCLUSIONS: Our study found that the incidence of genital warts was highest among persons aged 20 to 24 years using a unique method to identify the location of the wart. Information on incidence of genital warts before vaccine use provides baseline data that can be used to measure HPV vaccine impact.

Pharmacokinetics of a multipurpose pod-intravaginal ring simultaneously delivering five drugs in an ovine model.

Multipurpose technologies that simultaneously protect from sexually transmitted infections and unintended pregnancy are urgently needed. Pod-intravaginal rings (IVRs) formulated with the antiretroviral agents (ARVs) tenofovir, nevirapine, and saquinavir and the contraceptives etonogestrel and estradiol were evaluated in sheep. Steady-state concentrations were maintained for 28 days with controlled, sustained delivery. This proof-of-principle study demonstrates that pod IVRs can deliver three ARVs from different mechanistic classes and a progestin-estrogen combination over the wide range needed for putative preventative efficacy.

Integrated behavioral intervention to improve HIV/AIDS treatment adherence and reduce HIV transmission.

OBJECTIVES: We conducted a randomized clinical trial to test an integrated behavioral intervention designed to enhance using HIV treatment as prevention by improving medication adherence, reducing risks for other sexually transmitted infections, and minimizing risk compensation beliefs. METHODS: Individuals living with HIV/AIDS (n = 436) participated in a randomized clinical trial testing an intensive behavioral intervention aimed at reducing HIV transmission risks compared with an attention control condition. We used unannounced pill counts to monitor antiretroviral therapy adherence and computerized interviews to measure risk behaviors. RESULTS: The integrated transmission risk reduction intervention demonstrated increased antiretroviral therapy adherence and less unprotected intercourse with nonseroconcordant partners at 3- and 6-month follow-ups as well as fewer new sexually transmitted infections diagnosed over the 9-month follow-up period (adjusted odds ratio = 3.0; P < .05; 95% confidence interval = 1.01, 9.04). The integrated intervention also reduced behavioral risk compensation beliefs. CONCLUSIONS: A theory-based integrated behavioral intervention can improve HIV treatment adherence and reduce HIV transmission risks. HIV treatment as prevention should be bundled with behavioral interventions to maximize effectiveness.

Antiretroviral-based HIV prevention strategies for women.

Almost three decades have elapsed since researchers identified HIV as the cause of AIDS, with current estimates from UNAIDS that 33.4 million adults were living with HIV/AIDS in 2008. Two-thirds of this burden of disease is in Sub-Saharan Africa, and 60% of those infected are women. The disease still remains incurable and current prevention strategies including abstinence, male/female condom use and male circumcision are only partially effective. New strategies to curb the epidemic are urgently needed. Scientists are diligently exploring HIV prevention methods that are safe, effective and affordable. These new biological interventions include oral pre-exposure prophylaxis using oral antiretroviral (ARV) drugs, ARV treatment in HIV-infected persons to reduce transmission and topical ARV-based microbicide formulations.

Public vaccination programmes against hepatitis B in The Netherlands: assessing whether a targeted or a universal approach is appropriate.

To date, the policy to control hepatitis B in the Netherlands is to vaccinate specific risk groups, rather than all children. Low incidence of the disease has fueled debate whether such a targeted vaccination strategy or rather a universal strategy, as recommended by the World Health Organization, is appropriate. The standard framework for assessing whether a particular vaccination should be included in a public programme, as recently proposed by the Health Council of the Netherlands (HCN), was applied to the various options for hepatitis B vaccination. This framework includes seven selection criteria, grouped under five thematic headings: seriousness and extent of the disease burden, effectiveness and safety of the vaccination, acceptability of the vaccination, efficiency of the vaccination, and priority of the vaccination. From about 1990 the disease burden has stayed more or less the same over time and careful assessment has made it clear that the targeted approach has failed to reach a significant part of the risk groups. Models suggest that the public health benefits obtained through targeted programmes could be augmented considerably by universal vaccination. Based on the assessment that universal vaccination means better protection for high-risk groups as well as the whole population, the HCN calls for universal immunisation, even though hepatitis B to a large extent is limited to specific high-risk groups. Should the Netherlands adopt universal vaccination, several immunisation programmes targeted to high-risk groups will, however, remain of crucial importance for years to come.

Prevention of vaginal simian immunodeficiency virus transmission in macaques by postexposure prophylaxis with zidovudine, lamivudine and indinavir.

OBJECTIVE: To evaluate the efficacy of postexposure prophylaxis with a combination of zidovudine (ZDV), lamivudine (3TC) and indinavir (IDV), after vaginal exposure to HIV. DESIGN: : Experimental intravaginal exposure of female cynomolgus macaques to SIVmac251. METHODS: ZDV/3TC/IDV treatment was initiated 4 h after exposure and continued for 28 days. Groups of six animals received a placebo or a combination of oral ZDV (4.5 mg/kg), 3TC (2.5 mg/kg) and IDV (20 mg/kg) twice daily or subcutaneous ZDV (4.5 mg/kg) and 3TC (2.5 mg/kg) twice daily, and a higher dose of IDV (60 mg/kg) administered orally twice daily. RESULTS: In the placebo group, all animals were infected. Antiretroviral association protected one of the six animals if all drugs were administered orally and four of the six animals if ZDV and 3TC were administered subcutaneously and IDV was given orally at triple dose. In infected animals, viremia was significantly delayed and lowered in treated animals than in animals given placebo, and high CD4 cell counts were maintained in the treated animals, at least in the medium term. Antiretroviral dosages made in macaques receiving the same treatments showed that protection efficacy could be linked to antiretroviral plasmatic concentration. CONCLUSION: This study shows, for the first time in macaques, that the postexposure prophylaxis recommended for humans may be effective after vaginal exposure. Improvements in pharmacokinetic parameters significantly increased treatment efficiency.

[Update on the epidemiology, diagnosis and treatment of sexually-transmitted infections]. / Panorama actual de la epidemiología, diagnóstico y tratamiento de las infecciones de transmisión sexual.

In the last decade, cases of sexually-transmitted infections (STIs) have progressively increased in Europe. The reasons for this increase are unclear, but may involve changes in social behavior, migration and international travel, coupled with the emergence of risk groups that have not been taken into sufficient consideration to date. The routine use of molecular diagnostic techniques for many of these infections has solved many problems of sensitivity and the suitability of samples for microbiological diagnosis: non-invasive samples can be used, which has undoubtedly contributed to the increase in the number of cases. Moreover, molecular methods have also been introduced for antibiotic and antiviral susceptibility testing, as well as for molecular characterization of clinical isolates. All of these factors, together with the approval of the vaccine against the human papillomavirus, have changed the landscape of STIs across Europe.

The HIV/AIDS/STI situation in Lao People's Democratic Republic.

Lao People's Democratic Republic (Lao PDR) is a landlocked country with a population of 5.5 million and a total land area of 236,800 square kilometers. It has a population density of 23.3. It borders Thailand, Myanmar, China, Vietnam, and Cambodia. Its population distribution is 54.9% below the age of 20 years, and 27.8% aged between 20 and 39 years (NSC, 2002). Women comprise 49.5% of the overall population. 1 National Statistics Center, Basic Statics, 2002; National Statics Center, Population Census.

Considerations and development of topical microbicides to inhibit the sexual transmission of HIV.

The increased incidence of HIV/AIDS disease in women aged 15 - 49 years has identified the urgent need for a female-controlled, efficacious and safe vaginal topical microbicide. To meet this challenge, new topical microbicide candidates consisting of molecules or formulations that modify the genital environment (BufferGel, engineered Lactobacillus, over-the-counter lubricants), surfactants (C31D/Savvy, sodium dodecyl sulfate, sodium lauryl sulfate), polyanionic polymers (PRO 2000, beta-cyclodextrin, Carraguard, CAP, D2S, SPL-7013), proteins (cyanovirin-N, monoclonal antibodies, thromspondin-1 peptides, Pokeweed antiviral protein and others), reverse transcription inhibitors (PMPA [Tenofovir ]), UC-781, SJ-3366, DABO and thiourea) and other molecules (NCp7-specific virucides, chemokine receptor agonists/antagonists, WHI-05 and WHI-07) are currently being investigated for activity, safety and efficacy. This review will assess the development of these molecules in the context of cervicovaginal defences and the clinical failure of nonoxynol-9.

Polyherbal formulations with wide spectrum antimicrobial activity against reproductive tract infections and sexually transmitted pathogens.

PROBLEM: Recent reports indicate high incidence of genital infections, most of which are sexually transmitted. Although specific drugs and antibiotics are available for some, a safe spermicidal formulation with wide spectrum antimicrobial action would be a desirable addition to the presently available spermicides. METHODS: Formulations at different dilutions were tested in culture systems on standard strains and clinical isolates including some isolates resistant to drugs. The effect on (HSV)-2 and Chlamydia trachomatis was determined in vivo in progestin sensitized mice. The effect on HIV-1 was investigated in two standardized systems. RESULTS: Polyherbal cream inhibited the growth in culture of clinical isolates of Candida albicans, Candida krusei and Candida tropicalis. Both the polyherbal cream and the Praneem polyherbal pessary inhibited urinary tract Escherichia coli (including multidrug resistant strains), and Neisseria gonorrhoeae (including 2 strains resistant to penicillin). Both formulations manifested virucidal activity against HIV-1 at >2 and 50% dilutions (in two different test systems) on contact for 1-2 min. Intravaginal inoculation of the cream and the pessary suspensions before inoculation of the pathogen prevented lesions and vaginal transmission of HSV-2 and C. trachomatis in progestin sensitized mice. CONCLUSIONS: Polyherbal formulations have wide spectrum antibacterial, antifungal and antiviral effect against the tested sexually transmitted pathogens.