Anke Hemmerling

Misoprostol and declining abortion-related morbidity in Santo Domingo, Dominican Republic: a temporal association

Objective  To validate anecdotal reports that abortion‐related complications decreased in the Dominican Republic after the introduction of misoprostol into the country.

Phase 2a study assessing colonization efficiency, safety, and acceptability of Lactobacillus crispatus CTV-05 in women with bacterial vaginosis.

Background: Bacterial vaginosis (BV) is a common vaginal infection caused by a lack of endogenous lactobacilli and overgrowth of pathogens that frequently recurs following antibiotic treatment. Methods: A phase 2a study assessed colonization efficiency, safety, tolerability, and acceptability of Lactobacillus crispatus CTV-05 (LACTIN-V) administered by a vaginal applicator. Twenty-four women with BV were randomized in a 3:1 ratio of active product to placebo. Participants used LACTIN-V at 2 × 109 colony-forming units (cfu)/dose or placebo for 5 initial consecutive days, followed by a weekly application over 2 weeks. They returned for follow-up on Days 10 and 28. Results: Sixty-one percent of the 18 women randomized to the LACTIN-V group were colonized with L. crispatus CTV-05 at Day 10 or Day 28. Among LACTIN-V users with complete adherence to the study regimen, 78% were colonized at Day 10 or Day 28. Of the 120 adverse events (AEs) that occurred, 108 (90%) and 12 (10%) were of mild and moderate severity, respectively. AEs were evenly distributed between the LACTIN-V and placebo group. Of the total AEs, 93 (78%) were genitourinary in origin. The most common genitourinary AEs included vaginal discharge (46%), abdominal pain (46%), dysuria (21%), pollakiuria (21%), vaginal odor (21%), and genital pruritus (17%). No grade 3 or 4 AEs or serious AEs occurred and no deep epithelial disruption was seen during colposcopic evaluation. The product was well tolerated and accepted. Conclusions: LACTIN-V colonized well, and was safe and acceptable in women treated for BV.

Developing multipurpose reproductive health technologies: an integrated strategy.

Women worldwide confront two frequently concurrent reproductive health challenges: the need for contraception and for protection from sexually transmitted infections, importantly HIV/AIDS. While conception and infection share the same anatomical site and mode of transmission, there are no reproductive health technologies to date that simultaneously address that reality. Relevant available technologies are either contraceptive or anti-infective, are limited in number, and require different modes of administration and management. These “single-indication” technologies do not therefore fully respond to what is a substantial reproductive health need intimately linked to pivotal events in many womens lives. This paper reviews an integrated attempt to develop multipurpose prevention technologies—“MPTs”—products explicitly designed to simultaneously address the need for both contraception and protection from sexually transmitted infections. It describes an innovative and iterative MPT product development strategy with the following components: identifying different needs for such technologies and global variations in reproductive health priorities, defining “Target Product Profiles” as the framework for a research and development “roadmap,” collating an integrated MPT pipeline and characterizing significant pipeline gaps, exploring anticipated regulatory requirements, prioritizing candidates for problem-solving and resource investments, and implementing an ancillary advocacy agenda to support this breadth of effort.

Effects of bacterial vaginosis-associated bacteria and sexual intercourse on vaginal colonization with the probiotic Lactobacillus crispatus CTV-05.

Objective: Several fastidious bacteria have been associated with bacterial vaginosis (BV), but their role in lactobacilli recolonization failure is unknown. We studied the effect of 7 BV-associated bacterial species and 2 Lactobacillus species on vaginal colonization with Lactobacillus crispatus CTV-05 (LACTIN-V). Methods: Twenty-four women with BV were given a 5-day course of metronidazole vaginal gel and then randomized 3:1 to receive either LACTIN-V or placebo applied vaginally once daily for 5 initial consecutive days, followed by a weekly application over 2 weeks. Vaginal swabs for L. crispatus CTV-05 culture and 9 bacterium-specific 16S rRNA gene quantitative polymerase chain reaction assays were analyzed on several study visits for the 18 women receiving LACTIN-V. Results: Vaginal colonization with CTV-05 was achieved in 61% of the participants receiving LACTIN-V at either day 10 or day 28 visit and 44% at day 28. Participants not colonized with CTV-05 had generally higher median concentrations of BV-associated bacteria compared to those who colonized. Between enrollment and day 28, the median concentration of Gardnerella vaginalis minimally reduced from 104.5 to 104.3 16S rRNA gene copies per swab in women who colonized with CTV-05 but increased from 105.7 to 107.3 in those who failed to colonize (P = 0.19). Similarly, the median concentration of Atopobium spp. reduced from 102.7 16S rRNA gene copies per swab to below limit of detection in women who colonized with CTV-05, but increased from 102.7 to 106.6 in those who failed to colonize (P = 0.04). The presence of endogenous L. crispatus at enrollment was found to be significantly associated with a reduced odds of colonization with CTV-05 on day 28 (P = 0.003), and vaginal intercourse during the study significantly impaired successful CTV-05 colonization (P = 0.018). Conclusion: Vaginal concentration of certain BV-associated bacteria, vaginal intercourse during treatment, and the presence of endogenous L. crispatus at enrollment predict colonization with probiotic lactobacilli.

Phase 1 Dose-ranging Safety Trial of lactobacillus crispatus Ctv-05 for the Prevention of Bacterial Vaginosis

Background: Bacterial vaginosis is a very common vaginal infection. The lack of endogenous lactobacilli and overgrowth of pathogens facilitate numerous gynecological complications. Methods: A phase I dose-ranging safety trial tested the safety, tolerability, and acceptability of Lactobacillus crispatus CTV-05 (LACTIN-V) administered by vaginal applicator. Twelve healthy volunteers were enrolled in 3 blocks of 4 (5 × 108, 1 × 109, and 2 × 109 cfu/dose). Each block was randomized in a 3:1 ratio of active product to placebo. Participants used study product for 5 consecutive days, returned for follow-up on days 7 and 14, and had phone interviews on days 2 and 35. Results: All 12 participants took 5 doses and completed study follow-up. Overall, 45 adverse events (AEs) occurred, of which 31 (69%) were genitourinary (GU) AEs. GU AEs appeared evenly distributed between the 3 treatment blocks and between LACTIN-V and placebo arms. The most common GU AEs were vaginal discharge in 5 subjects (42%), abdominal pain in 4 subjects (33%), metrorrhagia in 4 subjects (33%), vulvovaginitis in 4 subjects (33%), vaginal candidiasis in 3 subjects (25%), and vaginal odor in 3 subjects (25%). Forty-one (91%) AEs were mild (grade 1) in severity. All 4 moderate AEs (grade 2) were unrelated to product use. No grade 3 or 4 AEs or serious adverse events (SAE) occurred. Laboratory parameters and colposcopy findings were within normal limits or clinically insignificant. The product was well-tolerated and accepted. Conclusion: All 3 dose levels of LACTIN-V appeared to be safe and acceptable in healthy volunteers.

Emotional impact and acceptability of medical abortion with mifepristone: A German experience

In Germany, four years of experience with mifepristone as an alternative procedure to surgical abortion have revealed a still reluctant use of the new method. In the public discussion, the more participatory role of the women in the abortion procedure is often feared to have negative consequences for the emotional processing of the event. This study compares the womens criteria for selecting a method and the psychological responses before and four weeks after medical or surgical abortion. Two hundred and nineteen women answered questions regarding demographic data, motivation, medical details and social support. Additionally, the women completed the Hospital Anxiety and Depression Scale (HADS) and the Impact of Event Scale (IES). There were no differences regarding sociodemographic and reproductive characteristics among both groups. Comparing data before and a month after the abortion, our study showed a significant decline of both anxiety and depression for both abortion methods. The medical group had significantly lower entrance levels of anxiety than the surgical group. The medical regimen caused significantly more sequelae such as prolonged bleeding, pain and other side effects. However, this did not have a negative influence on the coping process. A vast majority of women in both groups evaluated choosing between different abortion methods as being highly important to them. Our study supports the consensus view that termination of an unwanted pregnancy is a positive first solution to the conflict, regardless of the chosen method. The positive outcome and high satisfaction levels among the participants illustrate the importance of an ongoing and improved accessibility of medical abortion for women in Germany.

The worldwide burden of postpartum haemorrhage: Policy development where inaction is lethal

Most maternal deaths occur to women who are not attended by trained health professionals. Postpartum hemorrhage is the single most common cause of maternal death. The delivery of large haemochorial placenta in our species predisposes to heavy bleeding and can be dealt with only by using effective uterotonics. The 1987 Safe Motherhood Initiative has failed to reduce maternal mortality significantly, and shortages of trained personnel will not be remedied in the foreseeable future. Bold new policies are imperative and need to be derived from an appropriate evidence base. It is suggested that these should include the low‐cost shock garments in primary health facilities and making misoprostol easily accessible in both the public and private sector.

Ensuring successful development and introduction of multipurpose prevention technologies through an innovative partnership approach

Unintended pregnancies and the spread of sexually transmitted infections (STIs), including HIV, remain critical public health issues. Despite the apparent public health potential of comprehensive prevention methods, research and development for contraception and prevention of HIV and other STIs have historically remained separate because of different funding streams, policies and regulatory mechanisms. The result has led to missed opportunities to effectively and adequately address these interconnected sexual and reproductive health (SRH) risks. One global collaborative partnership to advance the comprehensive SRH prevention field is the Initiative for Multipurpose Prevention Technologies (IMPT). Begun in 2009, the aim of this cross-sector initiative is to advance the development and eventual introduction of combination products for women that provide simultaneous protection from multiple SRH risks. To date, the IMPT has engaged product developers, scientific researchers, healthcare providers, funders and community-based advocates in China, India, the USA and across Africa and western Europe behind this common agenda. The IMPT defines multipurpose prevention technologies (MPTs) as products that combine protection against unintended pregnancy and STIs, including HIV. The vision for MPTs is a suite of accessible products that are womaninitiated, efficient and easy to use. MPTs currently in development include intravaginal rings that combine a contraceptive hormone with anti-viral drugs for HIV and herpes simplex virus type 2 prevention; on-demand products such as a diaphragm loaded with an anti-HIV drug; and co-administered or co-formulated multipurpose injectables. These products could represent a powerful means of achieving high public health impact in at-risk populations around the world. The IMPT is in its fifth year and is navigating the boundaries of collaborative decision-making around a complex product development agenda. This editorial describes the structured and innovative approach developed by the Initiative to facilitate MPT development, funding and introduction.

Women Front and Center: The Opportunities of Involving Women in Participatory Health Research Worldwide

Participatory research involving communities, especially women, is increasingly recognized as a valuable and scientifically sound approach to improve the relevance of a study, the accuracy of data collection and interpretation, the adherence to study procedures, and the likelihood of adopting any resulting intervention. This approach has interdisciplinary roots dating back more than half a century. Although widely used in community-based conservation and development projects worldwide, international public health research has yet to fully embrace this inclusive approach, which requires the sharing of power with research participants and a more involved relationship building process with communities. In return, the gap between publication and public action can be narrowed because ownership of the research process by an empowered community can lay the foundation for an accelerated implementation of interventions tailored to community needs and based on research results. This article draws on the professional experiences of the authors as well as published examples of international participatory health research with women. Factors critical for the success of participatory research are discussed, including attention to initial planning, early community involvement, conceptual clarity, defined community benefits, and joint interpretation of results, as well as translation to action. It includes common challenges and strategies to overcome them, such as conflict resolution and data ownership.

Trypan blue staining to determine vaginal exposure in two types of plastic vaginal applicators containing two different microbicide formulations.

Dye staining of applicators has been shown to be a reliable and objective method to test vaginal insertion in clinical microbicide trials, but different plastics, dyes, and product formulations may impact the accuracy of this method. Reportedly used applicators returned from 3 clinical trials were stained with 1% trypan blue. In a phase 1 study (VivaGel), using gel-filled HTI polypropylene applicators, 1271 (97%) of applicators stained positive. In a phase 1 and a phase 2a study (LACTIN-V) using linear low-density polyethylene applicators to deliver a dry powder formulation, 57 (95%) and 135 (86%) tested positive, respectively. Dye staining of vaginal applicators is an objective low-cost measure suitable for low-resource settings.