Inflammatory cytokine biomarkers to identify women with asymptomatic sexually transmitted infections and bacterial vaginosis who are at high risk of HIV infection.
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.
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.
Lindi
L
Masson
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Kelly B
KB
Arnold
Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa.
Francesca
F
Little
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.
Koleka
K
Mlisana
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.
David A
DA
Lewis
National Institute for Communicable Diseases, Sandringham, Johannesburg, South Africa.
Nonhlanhla
N
Mkhize
Institute of Infectious Diseases and Molecular Medicine, University of Cape Town Medical School, Cape Town, South Africa.
Hoyam
H
Gamieldien
Centre for the AIDS Programme of Research in South Africa, University of KwaZulu Natal, Durban, South Africa.
Sinaye
S
Ngcapu
Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
Leigh
L
Johnson
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Douglas A
DA
Lauffenburger
Centre for the AIDS Programme of Research in South Africa, University of KwaZulu Natal, Durban, South Africa Columbia University, New York, New York, USA.
Quarraisha
Q
Abdool Karim
Centre for the AIDS Programme of Research in South Africa, University of KwaZulu Natal, Durban, South Africa Columbia University, New York, New York, USA.
Salim S
SS
Abdool Karim
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.
Jo-Ann S
JA
Passmore
D000293:Adolescent; D015415:Biomarkers / Q000032:analysis; D018797:Cell Cycle Proteins / Q000235:genetics; D002584:Cervix Uteri / Q000737:chemistry*; D054357:Chemokine CXCL10 / Q000032:analysis; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000032:analysis*; D005260:Female; D015658:HIV Infections / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D053583:Interleukin-1beta / Q000032:analysis; D016015:Logistic Models; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D012680:Sensitivity and Specificity; D012749:Sexually Transmitted Diseases / Q000150:complications / Q000175:diagnosis*; D007507:Therapeutic Irrigation; D014621:Vagina / Q000737:chemistry*; D016585:Vaginosis, Bacterial / Q000150:complications / Q000175:diagnosis*; D055815:Young Adult
D015415:Biomarkers; D018797:Cell Cycle Proteins; D054357:Chemokine CXCL10; D016207:Cytokines; D053583:Interleukin-1beta; C497749:TSPY1 protein, human
BACTERIAL VAGINOSIS; DIAGNOSIS; GENITAL TRACT INFECT; INFLAMMATION; WOMEN