Lindi Masson1, Kelly B Arnold2, Francesca Little3, Koleka Mlisana4, David A Lewis5, Nonhlanhla Mkhize6, Hoyam Gamieldien7, Sinaye Ngcapu8, Leigh Johnson9, Douglas A Lauffenburger2, Quarraisha Abdool Karim10, Salim S Abdool Karim10, Jo-Ann S Passmore11. 1. Institute of Infectious Diseases and Molecular Medicine, University of Cape Town Medical School, Cape Town, South Africa Centre for the AIDS Programme of Research in South Africa, University of KwaZulu Natal, Durban, South Africa. 2. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. 3. Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa. 4. Centre for the AIDS Programme of Research in South Africa, University of KwaZulu Natal, Durban, South Africa School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal. 5. Western Sydney Sexual Health Centre, Parramatta, Australia Centre for Infectious Diseases and Microbiology & Marie Bashir Institute for Infectious Diseases and Biosecurity, Westmead Clinical School, University of Sydney, Sydney, Australia National Institute for Communicable Diseases, Sandringham, Johannesburg, South Africa. 6. National Institute for Communicable Diseases, Sandringham, Johannesburg, South Africa. 7. Institute of Infectious Diseases and Molecular Medicine, University of Cape Town Medical School, Cape Town, South Africa. 8. Centre for the AIDS Programme of Research in South Africa, University of KwaZulu Natal, Durban, South Africa. 9. Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. 10. Centre for the AIDS Programme of Research in South Africa, University of KwaZulu Natal, Durban, South Africa Columbia University, New York, New York, USA. 11. Institute of Infectious Diseases and Molecular Medicine, University of Cape Town Medical School, Cape Town, South Africa Centre for the AIDS Programme of Research in South Africa, University of KwaZulu Natal, Durban, South Africa National Health Laboratory Services, South Africa.
Abstract
BACKGROUND: Untreated sexually transmitted infections (STIs) and bacterial vaginosis (BV) cause genital inflammation and increase the risk of HIV infection. WHO-recommended syndromic STI and BV management is severely limited as many women with asymptomatic infections go untreated. The purpose of this cross-sectional study was to evaluate genital cytokine profiles as a biomarker of STIs and BV to identify women with asymptomatic, treatable infections. METHODS: Concentrations of 42 cytokines in cervicovaginal lavages from 227 HIV-uninfected women were measured using Luminex. All women were screened for BV by microscopy and STIs using molecular assays. Multivariate analyses were used to identify cytokine profiles associated with STIs/BV. RESULTS: A multivariate profile of seven cytokines (interleukin (IL)-1α, IL-1β, tumour necrosis factor-β, IL-4, fractalkine, macrophage-derived chemokine, and interferon-γ) most accurately predicted the presence of a treatable genital condition, with 77% classification accuracy and 75% cross-validation accuracy (sensitivity 72%; specificity 81%, positive predictive value (PPV) 86%, negative predictive value (NPV) 64%). Concomitant increased IL-1β and decreased IP-10 concentrations predicted the presence of a treatable genital condition without a substantial reduction in predictive value (sensitivity 77%, specificity 72%, PPV 82% and NPV 65%), correctly classifying 75% of the women. This approach performed substantially better than clinical signs (sensitivity 19%, specificity 92%, PPV 79% and NPV 40%). CONCLUSIONS: Supplementing syndromic management with an assessment of IL-1β and IP-10 as biomarkers of genital inflammation may improve STI/BV management for women, enabling more effective treatment of asymptomatic infections and potentially reducing their risk of HIV infection. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
BACKGROUND: Untreated sexually transmitted infections (STIs) and bacterial vaginosis (BV) cause genital inflammation and increase the risk of HIV infection. WHO-recommended syndromic STI and BV management is severely limited as many women with asymptomatic infections go untreated. The purpose of this cross-sectional study was to evaluate genital cytokine profiles as a biomarker of STIs and BV to identify women with asymptomatic, treatable infections. METHODS: Concentrations of 42 cytokines in cervicovaginal lavages from 227 HIV-uninfected women were measured using Luminex. All women were screened for BV by microscopy and STIs using molecular assays. Multivariate analyses were used to identify cytokine profiles associated with STIs/BV. RESULTS: A multivariate profile of seven cytokines (interleukin (IL)-1α, IL-1β, tumour necrosis factor-β, IL-4, fractalkine, macrophage-derived chemokine, and interferon-γ) most accurately predicted the presence of a treatable genital condition, with 77% classification accuracy and 75% cross-validation accuracy (sensitivity 72%; specificity 81%, positive predictive value (PPV) 86%, negative predictive value (NPV) 64%). Concomitant increased IL-1β and decreased IP-10 concentrations predicted the presence of a treatable genital condition without a substantial reduction in predictive value (sensitivity 77%, specificity 72%, PPV 82% and NPV 65%), correctly classifying 75% of the women. This approach performed substantially better than clinical signs (sensitivity 19%, specificity 92%, PPV 79% and NPV 40%). CONCLUSIONS:Supplementing syndromic management with an assessment of IL-1β and IP-10 as biomarkers of genital inflammation may improve STI/BV management for women, enabling more effective treatment of asymptomatic infections and potentially reducing their risk of HIV infection. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Entities:
Keywords:
BACTERIAL VAGINOSIS; DIAGNOSIS; GENITAL TRACT INFECT; INFLAMMATION; WOMEN
Authors: Ken S Lau; Alwin M Juchheim; Kimberly R Cavaliere; Sarah R Philips; Douglas A Lauffenburger; Kevin M Haigis Journal: Sci Signal Date: 2011-03-22 Impact factor: 8.192
Authors: Koleka Mlisana; Nivashnee Naicker; Lise Werner; Lindi Roberts; Francois van Loggerenberg; Cheryl Baxter; Jo-Ann S Passmore; Anneke C Grobler; A Willem Sturm; Carolyn Williamson; Katharina Ronacher; Gerhard Walzl; Salim S Abdool Karim Journal: J Infect Dis Date: 2012-04-19 Impact factor: 5.226
Authors: Jill S Huppert; Regina G Taylor; Sarah St Cyr; Elizabeth A Hesse; Jennifer L Reed Journal: Sex Transm Infect Date: 2013-03-07 Impact factor: 3.519
Authors: Catia T Perciani; Bashir Farah; Rupert Kaul; Mario A Ostrowski; Salaheddin M Mahmud; Omu Anzala; Walter Jaoko; Kelly S MacDonald Journal: J Clin Invest Date: 2019-01-22 Impact factor: 14.808
Authors: Maria Trent; Jamie Perin; Julia Rowell; Maunank Shah; Jennifer Anders; Pamela Matson; Rebecca M Brotman; Jacques Ravel; Phyllis Sharps; Richard Rothman; Hasiya E Yusuf; Charlotte A Gaydos Journal: J Infect Dis Date: 2021-08-16 Impact factor: 7.759
Authors: Javier R Lama; Shelly T Karuna; Shannon P Grant; Edith M Swann; Carmela Ganoza; Patricia Segura; Silvia M Montano; Martin Lacherre; Stephen C De Rosa; Susan Buchbinder; Jorge Sanchez; M Juliana McElrath; Maria P Lemos Journal: PLoS One Date: 2016-08-18 Impact factor: 3.240
Authors: Kristin M Wall; William Kilembe; Bellington Vwalika; Lisa B Haddad; Eric Hunter; Shabir Lakhi; Roy Chavuma; Naw Htee Khu; Ilene Brill; Cheswa Vwalika; Lawrence Mwananyanda; Elwyn Chomba; Joseph Mulenga; Amanda Tichacek; Susan Allen Journal: Int J Epidemiol Date: 2017-10-01 Impact factor: 7.196
Authors: Vicky Jespers; Jordan Kyongo; Sarah Joseph; Liselotte Hardy; Piet Cools; Tania Crucitti; Mary Mwaura; Gilles Ndayisaba; Sinead Delany-Moretlwe; Jozefien Buyze; Guido Vanham; Janneke H H M van de Wijgert Journal: Sci Rep Date: 2017-09-20 Impact factor: 4.379
Authors: Shameem Z Jaumdally; Lindi Masson; Heidi E Jones; Smritee Dabee; Donald R Hoover; Hoyam Gamieldien; Nontokozo Langwenya; Landon Myer; Catherine S Todd; Jo-Ann S Passmore Journal: Sci Rep Date: 2018-08-15 Impact factor: 4.379