Alexander Munoz1,2, Matthew R Hayward1,2, Seth M Bloom1,2,3, Muntsa Rocafort1, Sinaye Ngcapu4,5, Nomfuneko A Mafunda1, Jiawu Xu1, Nondumiso Xulu6, Mary Dong1,7,8, Krista L Dong1,7,8, Nasreen Ismail6, Thumbi Ndung'u1,6,9,10,11, Musie S Ghebermichael1, Douglas S Kwon12,13,14. 1. Ragon Institute of MGH, MIT, and Harvard, 400 Technology Square, Cambridge, MA, 02139, USA. 2. Harvard Medical School, Boston, MA, 02115, USA. 3. Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, 02114, USA. 4. Centre for the AIDS Programme of Research in South Africa (CAPRISA), Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. 5. Department of Medical Microbiology, University of KwaZulu-Natal, Durban, South Africa. 6. HIV Pathogenesis Programme (HPP), Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. 7. Females Rising through Education, Support, and Health, Durban, KwaZulu-Natal, South Africa. 8. Massachusetts General Hospital, Boston, MA, 02114, USA. 9. Africa Health Research Institute (AHRI), Durban, South Africa. 10. Max Planck Institute for Infection Biology, Berlin, Germany. 11. Division of Infection and Immunity, University College London, London, United Kingdom. 12. Ragon Institute of MGH, MIT, and Harvard, 400 Technology Square, Cambridge, MA, 02139, USA. dkwon@mgh.harvard.edu. 13. Harvard Medical School, Boston, MA, 02115, USA. dkwon@mgh.harvard.edu. 14. Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, 02114, USA. dkwon@mgh.harvard.edu.
Abstract
BACKGROUND: Cervicovaginal bacterial communities composed of diverse anaerobes with low Lactobacillus abundance are associated with poor reproductive outcomes such as preterm birth, infertility, cervicitis, and risk of sexually transmitted infections (STIs), including human immunodeficiency virus (HIV). Women in sub-Saharan Africa have a higher prevalence of these high-risk bacterial communities when compared to Western populations. However, the transition of cervicovaginal communities between high- and low-risk community states over time is not well described in African populations. RESULTS: We profiled the bacterial composition of 316 cervicovaginal swabs collected at 3-month intervals from 88 healthy young Black South African women with a median follow-up of 9 months per participant and developed a Markov-based model of transition dynamics that accurately predicted bacterial composition within a broader cross-sectional cohort. We found that Lactobacillus iners-dominant, but not Lactobacillus crispatus-dominant, communities have a high probability of transitioning to high-risk states. Simulating clinical interventions by manipulating the underlying transition probabilities, our model predicts that the population prevalence of low-risk microbial communities could most effectively be increased by manipulating the movement between L. iners- and L. crispatus-dominant communities. CONCLUSIONS: The Markov model we present here indicates that L. iners-dominant communities have a high probability of transitioning to higher-risk states. We additionally identify transitions to target to increase the prevalence of L. crispatus-dominant communities. These findings may help guide future intervention strategies targeted at reducing bacteria-associated adverse reproductive outcomes among women living in sub-Saharan Africa. Video Abstract.
BACKGROUND: Cervicovaginal bacterial communities composed of diverse anaerobes with low Lactobacillus abundance are associated with poor reproductive outcomes such as preterm birth, infertility, cervicitis, and risk of sexually transmitted infections (STIs), including human immunodeficiency virus (HIV). Women in sub-Saharan Africa have a higher prevalence of these high-risk bacterial communities when compared to Western populations. However, the transition of cervicovaginal communities between high- and low-risk community states over time is not well described in African populations. RESULTS: We profiled the bacterial composition of 316 cervicovaginal swabs collected at 3-month intervals from 88 healthy young Black South African women with a median follow-up of 9 months per participant and developed a Markov-based model of transition dynamics that accurately predicted bacterial composition within a broader cross-sectional cohort. We found that Lactobacillus iners-dominant, but not Lactobacillus crispatus-dominant, communities have a high probability of transitioning to high-risk states. Simulating clinical interventions by manipulating the underlying transition probabilities, our model predicts that the population prevalence of low-risk microbial communities could most effectively be increased by manipulating the movement between L. iners- and L. crispatus-dominant communities. CONCLUSIONS: The Markov model we present here indicates that L. iners-dominant communities have a high probability of transitioning to higher-risk states. We additionally identify transitions to target to increase the prevalence of L. crispatus-dominant communities. These findings may help guide future intervention strategies targeted at reducing bacteria-associated adverse reproductive outcomes among women living in sub-Saharan Africa. Video Abstract.
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