Bacterial vaginosis among women at high risk for HIV in East Africa: the role of behaviour, host immunity, genetics

Around 25 million people are infected with the human immunodeficiency virus (HIV) in sub-Saharan Africa - roughly two-thirds of the worldwide total. The greatest burden is shouldered by 13.3 million African women, who make up 60% of the epidemic in this region. A risk factor for HIV, bacterial vaginosis (BV) is a highly prevalent, reproductive tract infection affecting women. We do not understand the causes of BV or how to control it long-term.

By further investigating behaviour, genetics, and immunological responses to BV, as well as the bacteria that are associated with BV, we hope to further understand the role of these factors in BV and develop a framework that would help researchers to design interventions to respond to this infection. Though research has shown that some types of behaviour are risk factors for BV, notably intravaginal cleansing and sexual behaviour (e.g. new sex partners, frequency of sexual intercourse without condoms), it seems that behaviour does not completely explain the following questions: why some populations have consistently higher prevalence of BV than others; why some women have recurrent BV and others do not; and why some women have symptoms and others do not. We hope to find answers to these questions that will guide future research on BV with the aim of reducing reproductive health burden and HIV transmission.

Aims:
1) To investigate the role of behavioural, genetic and immunological risk factors for bacterial vaginosis as well as BV-associated bacteria in a population of women at high-risk for HIV in Tanzania.
2) To develop a comprehensive framework for further research related to BV that would include each of the above factors and their interactions, and contribute to the development of interventions against BV.

Objectives:
1) To investigate the prevalence of BV in two large observational cohorts, and to identify social and behavioural factors related to BV, symptomatic infection and recurrence
2) To describe the vaginal flora in women with and without BV
3) To investigate the immunological response and gene expression in women with and without BV
4) To finalise a conceptual framework to inform future epidemiological studies investigating BV

Design: Secondary analyses of data from three observational cohorts and the testing and analysis of stored specimens.

Methodology: This work will exploit the data previously collected from several studies in North-West Tanzania including the EDCTP-funded Women‘s Health Project (WHP), the MRC-funded Inflammation Sub-study, and MDP 301 feasibility study. With these data, we will be able to do in-depth analyses of the correlates of BV and recurrence, description and correlates of BV-specific bacteria, and description of immune responses associated with BV or BV-specific bacteria.

In addition, the WHP has preserved 230 CVL cell pellets from participants attending for their 12 month (final) visit. Samples will be sequenced for selected bacteria using semi-quantitative methods, and then tested for human gene expression.

With the outputs from the above analyses, I will employ advanced epidemiological methods including causal inference and infectious disease modelling to develop a conceptual framework for future research on BV.

Scientific and medical opportunities: Detailed research on BV has not been carried out previously among women at high risk for HIV in sub-Saharan Africa. This research would take advantage of previously collected data to analyse correlates of BV and recurrent BV, identify BV-associated bacteria and obtain detailed data on vaginal mucosal immunity. In addition, we will be able to carry out human genome-wide expression studies that will provide a comprehensive picture of the genes and immune pathways activated during BV. With the outputs from these analyses, I will be able to develop future strategies for research projects including intervention studies on the treatment or prevention of BV with the aim of reducing reproductive health burden and HIV transmission.