Injectable contraceptives: Good or Bad? Léanie Kleynhans Supervisor: Dr Katharina Ronacher Department of Biomedical Sciences University of Stellenbosch SUN Immunology Research Group SUN Immunology Research Group

(Medroxyprogesterone Acetate) MPA 3 months injectable contraceptive R6,03 Connect last sentence in first section with second section SUN Immunology Research Group (Medroxyprogesterone Acetate)

Medroxyprogesterone Acetate (Norethisterone enanthate) NET 2 months injectable contraceptive R12,91 Connect last sentence in first section with second section (Norethisterone enanthate) SUN Immunology Research Group

What do we know about MPA? Makes women more prone to HIV Increased number of HIV viruses in vagina Increases risk of spreading HIV to male partners Functions in similar way as the stress hormone cortisol SUN Immunology Research Group

MPA most commonly used contraceptive in areas with high TB infection rates Contraceptives used in TB household contacts Ravensmead/Uitsig, Cape Town SUN Immunology Research Group

Our study MPA MPA and TB-causing bacteria added to blood in artificial system. Extracted blood from MPA users and non-contraceptive users. Added TB-causing bacteria. 3 Injected MPA and TB-causing bacteria into mice to investigated the development disease. MPA vs SUN Immunology Research Group

1. MPA alters the functioning of immune cells HUMAN STUDY: MPA Levels of immune “messengers” Expression level (Kleynhans et al. 2011 PLoS ONE 6:e24639) SUN Immunology Research Group

2. MPA-use alters functioning of immune cells in women using this contraceptive vs Expression level Levels of immune “messengers” (Kleynhans et al. 2011 PLoS ONE 6:e24639) SUN Immunology Research Group

3. MPA users have lower levels of immune cells called monocytes vs Monocytes Group: p = 0.0033 Time: p = 0.1638 log10 Monocytes R F6 F18 Time point 0.73 0.74 0.75 0.76 0.77 0.78 0.79 0.80 0.81 0.82 0.83 Cell numbers Immune cells: monocytes MPA users Controls Time (Kleynhans et al. 2011 PLoS ONE 6:e24639) SUN Immunology Research Group

Collect lung tissue MOUSE STUDY: Day 8: TB Infection Day 1: MPA 3 weeks 8 weeks 16 weeks Collect lung tissue SUN Immunology Research Group

4. Mice injected with MPA and TB bacteria have more bacteria in their lungs Bacterial load Bacteria in lungs TB TB + MPA SUN Immunology Research Group

Does NET alter the functioning of immune cells? Levels of immune “messengers” Expression level SUN Immunology Research Group

Are injectable contraceptives good or bad? Take home message… MPA limits normal functioning of certain immune cells MPA users have lower levels of the immune cells called monocytes Mice injected with MPA have more bacteria in their lungs than untreated mice NET does not limit immune functions Are injectable contraceptives good or bad? SUN Immunology Research Group

National Research Foundation Harry Crossley Acknowledgements Collaborators at UCT Prof Muazzam Jacobs Dr Nasiema Allie Dr Petrus Steyn Funding National Research Foundation Harry Crossley South Africa TB AIDS Training Program (SATBAT) KwaZulu-Natal Research Institute for TB-HIV (K-RITH) Bill and Melinda Gates Foundation Dr Katharina Ronacher Prof Gerhard Walzl Nelita du Plessis Lizaan Ehlers Prof Martin Kidd SUN Immunology Research Group