The long term objective of this research is to achieve a more rational, realistic paradigm of vaginal bacterial species and their influence on health and disease. Relevance: Bacterial Vaginosis (BV) is the most frequent cause of gynecological visits relating to vaginal irritation. More significantly, this very common ailment is associated with severe sequelae including preterm delivery and increased risk of HIV infection. BV is a microbiologic enigma. It appears to be a change in bacterial species that colonize the vaginal epithelium rather than a true tissue infection by a specific pathogen, however the cause is unknown. Standard treatment with metronidazole often fails, and recurrence rates are high. The fact that currently recommended therapy is relatively ineffective may explain why antibiotic treatment trials directed at preventing the complications of BV have failed. While evidence from studies of virgins suggests BV can arise endogenously, studies of sexually active women strongly suggest it is sexually transmitted. Recurrent infection rates following treatment are high and though partner treatment appears not to reduce these rates, the data strongly suggest that the male plays a role in re introducing BV associated organisms into the vagina. Insight: Recent cultivation-independent PCR analyses of vaginal flora have shown that the vaginal micro environment is much more complex than previously understood. Molecular tools are now available begin to better understand the etiology of BV, how it causes human disease and why current treatment is so inadequate. Hypothesis: BV treatment failures are associated with here-to-fore unstudied, uniquely definable, bacterial species consortia while recurrence is related to sexual contact with male partners who harbor these previously unknown BV-associated species.
Specific Aims : (1) A panel of twenty species-specific quantitative real time PCR assays will be used to obtain detailed profiles of bacterial species-composition, and relative abundance, in women with clinically defined BV and in their male partners. (2) A cohort of monogamous women receiving oral metronidazole for treatment of BV, and their untreated male partners, will be followed to determine correlations between microbial species composition, treatment failure and recurrent BV. These analyses will be controlled for behavioral factors that might influence outcomes as well as treatment compliance. Significance: The results should lead to more effective methods of diagnosing and treating BV, and preventing the serious sequelae associated with this common syndrome.

Public Health Relevance

Bacterial Vaginosis (BV) is the most frequent cause of gynecological visits relating to vaginal irritation. More significantly, this very common ailment is associated with severe sequelae including preterm delivery and increased risk of HIV infection. The results of this study should improve our understanding of vaginal bacterial flora in health and disease, and lead to more effective methods of diagnosing and treating bacterial vaginosis and preventing the serious sequelae associated with this common syndrome.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI079071-04
Application #
8261674
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
David, Hagit S
Project Start
2009-05-01
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2014-04-30
Support Year
4
Fiscal Year
2012
Total Cost
$469,129
Indirect Cost
$67,315
Name
Children's Hospital (New Orleans)
Department
Type
DUNS #
069523405
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Martin, David H; Zozaya, Marcela; Lillis, Rebecca A et al. (2013) Unique vaginal microbiota that includes an unknown Mycoplasma-like organism is associated with Trichomonas vaginalis infection. J Infect Dis 207:1922-31
Martin, David H (2012) The microbiota of the vagina and its influence on women's health and disease. Am J Med Sci 343:2-9
Eren, A Murat; Zozaya, Marcela; Taylor, Christopher M et al. (2011) Exploring the diversity of Gardnerella vaginalis in the genitourinary tract microbiota of monogamous couples through subtle nucleotide variation. PLoS One 6:e26732
Zozaya-Hinchliffe, Marcela; Lillis, Rebecca; Martin, David H et al. (2010) Quantitative PCR assessments of bacterial species in women with and without bacterial vaginosis. J Clin Microbiol 48:1812-9