Inflammatory cytokine biomarkers to identify women with asymptomatic sexually transmitted infections and bacterial vaginosis who are at high risk of HIV infection

Lindi Masson; Kelly B Arnold; Francesca Little; Koleka Mlisana; David A Lewis; Nonhlanhla Mkhize; Hoyam Gamieldien; Sinaye Ngcapu; Leigh Johnson; Douglas A Lauffenburger; Quarraisha Abdool Karim; Salim S Abdool Karim; Jo-Ann S Passmore

doi:10.1136/sextrans-2015-052072

Inflammatory cytokine biomarkers to identify women with asymptomatic sexually transmitted infections and bacterial vaginosis who are at high risk of HIV infection

Sex Transm Infect. 2016 May;92(3):186-93. doi: 10.1136/sextrans-2015-052072. Epub 2015 Oct 28.

Authors

Affiliations

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.

Keywords: BACTERIAL VAGINOSIS; DIAGNOSIS; GENITAL TRACT INFECT; INFLAMMATION; WOMEN.

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Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Biomarkers / analysis
Cell Cycle Proteins / genetics
Cervix Uteri / chemistry*
Chemokine CXCL10 / analysis
Cross-Sectional Studies
Cytokines / analysis*
Female
HIV Infections / etiology
HIV Infections / prevention & control
Humans
Interleukin-1beta / analysis
Logistic Models
Middle Aged
Predictive Value of Tests
ROC Curve
Sensitivity and Specificity
Sexually Transmitted Diseases / complications
Sexually Transmitted Diseases / diagnosis*
Therapeutic Irrigation
Vagina / chemistry*
Vaginosis, Bacterial / complications
Vaginosis, Bacterial / diagnosis*
Young Adult

Substances

Biomarkers
Cell Cycle Proteins
Chemokine CXCL10
Cytokines
Interleukin-1beta
TSPY1 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding