Tackling Infectious Diseases with Rapid Molecular Diagnosis and Innovative Prevention.

Infectious diseases (IDs) are a leading cause of death. The diversity and adaptability of microbes represent a continuing risk to health. Combining vision with passion, our transdisciplinary medical research team has been focussing its work on the better management of infectious diseases for saving human lives over the past five decades through medical discoveries and innovations that helped change the practice of medicine. The team used a multiple-faceted and integrated approach to control infectious diseases through fundamental discoveries and by developing innovative prevention tools and rapid molecular diagnostic tests to fulfill the various unmet needs of patients and health professionals in the field of ID. In this article, as objectives, we put in context two main research areas of ID management: innovative infection prevention that is woman-controlled, and the rapid molecular diagnosis of infection and resistance. We also explain how our transdisciplinary approach encompassing specialists from diverse fields ranging from biology to engineering was instrumental in achieving success. Furthermore, we discuss our vision of the future for translational research to better tackle IDs.

A Pre-Phase III Efficacy Trial of the Spermicide/Contraceptive Effect of the Invisible Condom, a Non-Hormonal Vaginal Gel, in Women from Canada.

OBJECTIVES: To evaluate the spermicidal efficacy of non-hormonal vaginal gel in vitro and in a post-coital test, and to evaluate its contraceptive efficacy in Canadian women of childbearing age. METHODS: We conducted single-centre trial to assess spermicidal and contraceptive efficacy of vaginal gel. Participants were healthy, sexually active women aged 18-49 years and their regular male sexual partners (30 couples). Measured outcomes included effect of vaginal gel on sperm motility in vitro, its effect on sperm in a post-coital test, and its effect on pregnancy prevention over 3 months. RESULTS: For in vitro spermicidal effect, 98% and 67% of sperm were immotile in the presence of the gel with sodium lauryl sulfate (gel-SLS) and gel alone, respectively. For the post-coital test, 99% and 93% of sperm were immotile in the presence of gel-SLS and gel alone, respectively. In the second part of trial, a total of 410 instances of vaginal intercourse in 95 menstrual cycles were protected (during 3-month period of gel-SLS use before each sexual intercourse with probability of 24 conceptions prevented according to Wilcox's table). Four women became pregnant during the study period; 2 during unprotected vaginal intercourse around the time of ovulation, and 2 attributed to user failure. CONCLUSION: Based on our results, the vaginal gel demonstrated important spermicidal and contraceptive effect. A larger phase III contraceptive efficacy trial is warranted. The vaginal gel may represent a non-hormonal spermicide/contraceptive option for women.

"Researcher for a Day": Creating and Shaping a New Generation of Scientific and Medical Researchers.

Science is the engine of prosperity, helping society respond to the important issues it faces. We are presently witnessing a worldwide decline in high school students' interest in science, regardless of gender. To overcome this problem, developing science promotion programs and activities that inspire young people to become the scientists of tomorrow is critical. We strongly believe in the leadership of research centers in creating such programs, which could have a significant impact on the next generation of scientists. Here we present the 'Researcher for a Day' program, which offers senior high school students immersion days in a scientific workplace dedicated to microbiology, as an example for other institutions that would like to implement such a program. Researcher for a Day has already helped more than 4,000 young students who are considering their career choices discover the world of science. Similar approaches could be implemented virtually anywhere to extend these efforts to promote science among young people.

Criibacterium bergeronii gen. nov., sp. nov., a new member of the family Peptostreptococcaceae, isolated from human clinical samples.

A rod-shaped, motile anaerobic bacterium, designated CCRI-22567T, was isolated from a vaginal sample of a woman diagnosed with bacterial vaginosis and subjected to a polyphasic taxonomic study. The novel strain was capable of growth at 30-42 °C (optimum, 42 °C), at pH 5.5-8.5 (optimum, pH 7.0-7.5) and in the presence of 0-1.5 % (w/v) NaCl (optimally at 0.5 % NaCl). The phylogenetic trees based on 16S rRNA gene sequences showed that strain CCRI-22567T forms a distinct evolutionary lineage independent of other taxa in the family Peptostreptococcaceae. Strain CCRI-22567T exhibited 90.1 % 16S rRNA gene sequence similarity to Peptoanaerobacter stomatis ACC19aT and 89.7 % to Eubacterium yurii subsp. schtitka ATCC 43716. The three closest organisms with an available whole genome were compared to strain CCRI-22567T for genomic relatedness assessment. The genomic average nucleotide identities (OrthoANIu) obtained with Peptoanaerobacter stomatis ACC19aT, Eubacterium yurii subsp. margaretiae ATCC 43715 and Filifactor alocis ATCC 35896T were 71.8, 70.3 and 69.6 %, respectively. Strain CCRI-22567T contained C18 : 1 ω9c and C18 : 1 ω9c DMA as the major fatty acids. The DNA G+C content of strain CCRI-22567T based on its genome sequence was 33.8 mol%. On the basis of the phylogenetic, chemotaxonomic and other phenotypic properties, strain CCRI-22567T is considered to represent a new genus and species within the family Peptostreptococcaceae, for which the name Criibacterium bergeronii gen. nov., sp. nov., is proposed. The type strain of Criibacterium bergeronii is CCRI-22567T (=LMG 31278T=DSM 107614T=CCUG 72594T).

Draft Genome Sequence of a Sporulating and Motile Strain of Lachnotalea glycerini Isolated from Water in Québec City, Canada.

Lachnotalea glycerini CCRI-19302 belongs to the genus Lachnotalea The strain was isolated from a water sample harvested in Québec City, Canada. The genome assembly comprised 4,694,231 bp, with 34.6% GC content. This is the first documentation to report the genome sequence of a sporulating and motile strain of L. glycerini.

Draft Genome Sequence of Romboutsia weinsteinii sp. nov. Strain CCRI-19649T Isolated from Surface Water.

Romboutsia weinsteinii sp. nov. CCRI-19649T belongs to the genus Romboutsia The strain was isolated from a water sample harvested in Québec City, Québec, Canada. The genome assembly comprised 4,134,593 bp with a 29.3% GC content. This is the first documentation that reports the genome sequence of R. weinsteinii.

Draft Genome Sequence of Romboutsia maritimum sp. nov. Strain CCRI-22766T, Isolated from Coastal Estuarine Mud.

The Romboutsia maritimum sp. nov. CCRI-22766T strain was isolated from coastal estuarine mud in New Zealand. The genome assembly comprised 2,854,352 bp, with 27.1% G+C content. This is the first documentation that reports the genome sequence of R. maritimum.

Draft Genome Sequence of Criibacterium bergeronii gen. nov., sp. nov., Strain CCRI-22567T, Isolated from a Vaginal Sample from a Woman with Bacterial Vaginosis.

Criibacterium bergeronii gen. nov., sp. nov., CCRI-22567 is the type strain of the new genus Criibacterium The strain was isolated from a woman with bacterial vaginosis. The genome assembly comprised 2,384,460 bp, with 34.4% G+C content. This is the first genome announcement of a strain belonging to the genus Criibacterium.

Universal vaginal applicator for the uniform distribution of vaginal gel and cream formulations: a magnetic resonance imaging study.

OBJECTIVE: Conventional vaginal applicators with a single apical hole do not distribute vaginal formulations homogenously and do not cover the entire vaginal and cervical mucosa. To overcome this problem and offer women further protection against vaginal infections, we designed a unique vaginal applicator with multiple apical and lateral holes. We have previously shown that the new applicator distributes an investigational vaginal gel homogenously over the entire vaginal and cervical mucosa. In this study, we investigated (using MRI) whether the new applicator works as well with marketed vaginal gels and creams. METHODS: Eighteen women participated in the study and six vaginal gels and creams were tested. Each woman used a marketed vaginal product with its own commercial applicator (CA) once and with our universal vaginal applicator (UVA) once to deliver the same product. The applications were separated by a one-week period. Pelvic MRI was performed immediately after vaginal application to evaluate the product's distribution and mucosal coverage. RESULTS: Immediately after application of the vaginal product, the UVA homogenously distributed the six products (3 gels and 3 creams) over the entire vaginal and cervical mucosa. On the other hand, the tested CA delivered four products (3 gels and 1 cream) mainly to the cervix and the upper vagina, but not to the mid and lower vagina; for the other two creams, the distribution was similar to that of UVA. Furthermore, the UVA received the highest acceptability score. CONCLUSION: The UVA can be used to deliver different vaginal gel and cream products homogenously throughout the vagina. This was the first time the UVA had been tested with marketed vaginal gels and creams. This applicator, giving uniform mucosal coverage and being highly acceptable, may help women to better protect themselves against sexually transmitted infections.

Objectif : Les applicateurs vaginaux conventionnels dotés d'un seul orifice apical ne permettent pas de distribuer les formulations vaginales de façon homogène et ne couvrent pas l'intégralité de la muqueuse vaginale et cervicale. Pour surmonter ce problème et offrir aux femmes davantage de protection contre les infections vaginales, nous avons conçu un applicateur vaginal unique en son genre doté de multiples orifices apicaux et latéraux. Nous avons déjà démontré que ce nouvel applicateur permettait de distribuer un gel vaginal expérimental de façon homogène sur l'intégralité de la muqueuse vaginale et cervicale. Dans le cadre de cette étude, nous nous sommes penchés (en ayant recours à l'IRM) sur la question de savoir si ce nouvel applicateur fonctionnait tout aussi bien dans le cas des crèmes et des gels vaginaux offerts sur le marché. Méthodes : Dix-huit femmes ont participé à l'étude et six crèmes et gels vaginaux ont été mis à l'essai. Chacune de ces femmes a utilisé à deux reprises un même produit vaginal offert sur le marché : une fois au moyen de l'applicateur commercial fourni par le fabricant (AC) et une autre fois au moyen de notre applicateur vaginal universel (AVU). Une période d'une semaine séparait ces deux applications. Une IRM pelvienne a été menée immédiatement à la suite de chacune de ces applications vaginales afin d'évaluer la distribution du produit et l'aire couverte en ce qui concerne la muqueuse. Résultats : Immédiatement à la suite de l'application du produit vaginal, nous avons constaté que l'utilisation de l'AVU permettait la distribution homogène des six produits (trois gels et trois crèmes) sur l'intégralité de la muqueuse vaginale et cervicale. En revanche, dans le cas de quatre des produits en question (trois gels et une crème), l'AC mis à l'essai a donné lieu à une distribution ayant principalement atteint le col utérin et la partie supérieure du vagin (excluant ainsi les parties intermédiaire et inférieure du vagin); pour ce qui est des deux autres crèmes, la distribution obtenue était semblable à celle qu'a permise l'AVU. De surcroît, l'AVU a obtenu le score d'acceptabilité le plus élevé. Conclusion : L'AVU peut être utilisé pour assurer l'administration de divers produits vaginaux en gel et en crème de façon homogène dans tout le vagin. Il s'agissait de la première mise à l'essai de l'AVU au moyen de crèmes et de gels vaginaux offerts sur le marché. Cet applicateur, qui permet de couvrir l'aire muqueuse de façon uniforme et qui compte une acceptabilité élevée, pourrait aider les femmes à mieux se protéger contre les infections transmissibles sexuellement.

The future of microbicides.

There is an urgent need to develop vaginal microbicides to empower women to better control their own sexual life and to protect themselves against HIV and other sexually transmitted infections (STIs). Prevention of STIs with its 330 million cases a year would have a great global health impact. Because of their anatomy, women are up to 8 times more susceptible than men to STIs including HIV. Women who can't negotiate condom use with their male partners have no means of protecting themselves from these infections. In the last few years, especially after the recent failures of several microbicides in Phase III trials, there was increasing pressure from those favoring the use of a more targeted approach to introduce marketed antiretroviral drugs (ARVs) into microbicides. This Pre-Exposure Prophylaxis (PrEP) concept which targets only HIV using specific ARVs contrasts with the primary approach of broad spectrum microbicides which aimed at offering universal protection against several sexually transmitted pathogens. However, before using ARVs as PrEP for HIV prevention, there are still many important issues to consider. In this article, we compare both strategies, while reviewing the last 15 years of microbicide research and its future.

A randomized, double-blind, placebo-controlled Phase II extended safety study of two Invisible Condom formulations in Cameroonian women.

BACKGROUND: Invisible Condom gel formulations being developed as microbicides to prevent the sexual transmission of HIV are advancing through the phases of clinical trials. The objectives of this study were to evaluate, after 8 weeks of vaginal application, the extended safety and acceptability of two Invisible Condom vaginal gel formulations: (i) the polymer alone and (ii) the polymer containing sodium lauryl sulfate (SLS) compared to placebo. STUDY DESIGN: This study is a randomized, doubled-blind, placebo-controlled Phase II extended safety study in healthy sexually active women from Yaoundé, Cameroon. Women were randomized into three gel arms: (i) placebo, (ii) polymer alone and (iii) polymer/SLS. Women applied gel intravaginally twice daily for 8 weeks. RESULTS: A total of 194 sexually active women applied placebo (n=41), polymer alone (n=76) and polymer/SLS (n=77). Invisible Condom gel formulations were well tolerated with no reported serious adverse events. The majority of reported adverse events were mild or moderate and mostly similar in all three arms, except for pelvic pain that was 10% higher in the polymer and polymer/SLS arms compared to placebo. Colposcopy showed neither genital ulceration nor mucosal lesions. Nugent score, H(2)O(2)-producing lactobacilli and vaginal pH were not affected by the study products. The gel formulations and applicator were generally acceptable and comfortable. CONCLUSION: This extended safety study showed that the Invisible Condom gel formulations and applicator were well tolerated and acceptable when applied intravaginally twice daily for 8 weeks. Thus, further phases of clinical development of Invisible Condom as a potential microbicide to prevent sexual transmission of HIV are warranted.

A randomized, double-blind, placebo-controlled safety and acceptability study of two Invisible Condom formulations in women from Cameroon.

BACKGROUND: The objectives of this clinical trial were to evaluate the safety, tolerance and acceptability of two gel formulations of the Invisible Condom: (i) the polymer alone and (ii) the polymer-containing sodium lauryl sulfate (SLS) compared to placebo when applied intravaginally with our unique applicator in sexually abstinent and active woman volunteers. STUDY DESIGN: A randomized, doubled-blind, placebo-controlled study in healthy women from Yaoundé, Cameroon. Two hundred sixty women were randomized into three gel arms: (a) gel alone, (b) gel plus SLS and (c) placebo gel. Thirty-seven sexually abstinent women applied gel intravaginally once a day for 14 days, while 75, 74 and 74 sexually active women applied gel intravaginally once, twice or three times daily for 14 days, respectively. RESULTS: Retention rate was high at 85% and 221 women applied the two products and the placebo for a total of 6005 times. Nugent score, H(2)O(2)-producing lactobacilli and vaginal pH were stable throughout the study and were not affected by the study products. Colposcopy showed neither genital ulceration nor mucosal lesions. No study product-related serious adverse events were reported. The majority of reported adverse events were mild or moderate and largely similar in all 3 arms. Satisfaction questionnaire showed that the gel formulations and applicator were generally comfortable and acceptable. CONCLUSION: The Invisible Condom formulations and applicator were found to be comfortable, well tolerated and acceptable when applied intravaginally once, twice or thrice daily for 14 days. Thus, expanded safety evaluation is warranted.

Distribution of a vaginal gel (Invisible Condom) before, during and after simulated sexual intercourse and its persistence when delivered by two different vaginal applicators: a magnetic resonance imaging study.

OBJECTIVE: The objective of this study was to evaluate the vaginal distribution of a microbicidal gel (Invisible Condom) before, during and after simulated intercourse using an artificial phallus. The gel was delivered using either a new proprietary vaginal applicator (PVA), which has multiple lateral and apical holes, or a commercial applicator (CA), which has a single apical hole. The persistence of the gel was evaluated up to 24 h after its administration. STUDY DESIGN: Nine women (five women using the PVA and four women using the CA) applied the vaginal gel once, and pelvic images were taken immediately after application. An artificial phallus was inserted and the women had 30 vaginal thrusts, then another set of images was taken while the phallus was still inside the vagina. On exit of the phallus, one more set of images was taken. Images were subsequently taken at 30 min, 2 h, 6 h and 24 h after gel application. RESULTS: Immediately after gel application, the PVA distributed the gel throughout the vaginal/cervical mucosae, while the CA delivered the gel only to the cervical area. During simulated intercourse, the phallus further pushed the gel delivered with the CA into the fornix, whereas it spread the gel delivered with the PVA more evenly throughout the mucosal surface. After simulated intercourse, both applicators gave similar gel distributions between 30 min and 6 h after application. However, at 24 h, using the PVA, only 5% of the gel persisted in the vagina, compared to 40% of the gel using the CA. DISCUSSION AND CONCLUSION: Using the new PVA, the Invisible Condom covered the vaginal/cervical mucosae before and during simulated intercourse, offering immediate protection, whereas only the cervical mucosa was covered using the CA. Forty percent of the gel persisted mostly in the upper vaginal/cervical area at 24 h following its administration with the CA, while only 5% of the gel was left using the PVA. The new applicator, with its unique design, ensures an even and immediate coating lasting throughout the first 6 h and could prevent potential microbicide vaginal toxicity at 24 h.

Safety, tolerance and acceptability of the Invisible Condom and its vaginal applicator in healthy women and their male sexual partners.

OBJECTIVES: The study was conducted to evaluate the safety and acceptability of the Invisible Condom when applied once or twice daily for 14 days in healthy women and their male sexual partners. STUDY DESIGN: Forty-one women and 23 men divided into three cohorts were enrolled. Cohort 1:14 sexually abstinent women applying gel twice daily for 14 days; Cohort 2:14 sexually active women with tubal ligation applying gel once daily for 14 days and their 14 sexual partners who did not use gel; Cohort 3:13 women on oral contraceptive applying gel once daily for 14 days and 9 of their sexual partners. RESULTS: No serious adverse events (AEs) were reported. Colposcopy showed no genital ulceration nor epithelial lesions. No major changes in vaginal flora or vaginal pH were detected. None of the women had to stop product application because of AEs. The majority of AEs were mild. Common AEs were itching, dryness, burning sensation, erythema and discharge. Satisfaction questionnaire showed that the gel and applicator were acceptable. CONCLUSION: The Invisible Condom and applicator were safe, well tolerated and acceptable when applied intravaginally for 14 days. Thus, expanded safety and effectiveness evaluation is warranted.

Thermoreversible gel formulation containing sodium lauryl sulfate as a potential contraceptive device.

The contraceptive properties of a gel formulation containing sodium lauryl sulfate were investigated in both in vitro and in vivo models. Results showed that sodium lauryl sulfate inhibited, in a concentration-dependent manner, the activity of sheep testicular hyaluronidase. Sodium lauryl sulfate also completely inhibited human sperm motility as evaluated by the 30-sec Sander-Cramer test. The acid-buffering capacity of gel formulations containing sodium lauryl sulfate increased with the molarity of the citrate buffers used for their preparations. Furthermore, experiments in which semen was mixed with undiluted gel formulations in different proportions confirmed their physiologically relevant buffering capacity. Intravaginal application of the gel formulation containing sodium lauryl sulfate to rabbits before their artificial insemination with freshly ejaculated semen completely prevented egg fertilization. The gel formulation containing sodium lauryl sulfate was fully compatible with nonlubricated latex condoms. Taken together, these results suggest that the gel formulation containing sodium lauryl sulfate could represent a potential candidate for use as a topical vaginal spermicidal formulation to provide fertility control in women.

Comparative study of mechanisms of herpes simplex virus inactivation by sodium lauryl sulfate and n-lauroylsarcosine.

The mechanisms of herpes simplex virus (HSV) inactivation by sodium lauryl sulfate (SLS) and n-lauroylsarcosine (LS), two anionic surfactants with protein denaturant potency, have been evaluated in cultured cells. Results showed that pretreatment of HSV type 1 (HSV-1) strain F and HSV-2 strain 333 with either surfactant inhibited, in a concentration- and time-dependent manner, their infectivities on Vero cells. SLS was a more potent inhibitor of HSV-2 strain 333 infectivity than LS with respect to the concentration (4.8-fold lower) and time (2.4-fold shorter) required to completely inactivate the virus. No inhibition of both herpesvirus strains infectivities was observed when Vero cells were pretreated with either surfactant. LS prevented the binding of HSV-2 strain 333 to cells without affecting the stable attachment and the rate of penetration into cells, whereas SLS exerted the opposite effect. Both SLS and LS inhibited, in a concentration-dependent manner, the HSV-2 strain 333-induced cytopathic effect, probably by affecting newly synthesized virions that come into contact with surfactant molecules present in culture medium. The pretreatment of HSV-2 strain 333 with specific combinations of SLS and LS concentrations inhibited the viral infectivity in a synergistic manner and resulted in only a small increase in their toxicities for exponentially growing Vero cells compared with that caused by each compound alone. Taken together, these results suggest that SLS and LS, alone or combined, could represent potent candidates as microbicides in topical vaginal formulations to prevent the transmission of herpes and possibly other pathogens that cause sexually transmitted diseases, including human immunodeficiency virus type 1.