{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T01:46:17Z","timestamp":1773193577078,"version":"3.50.1"},"reference-count":27,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008136","name":"Case Western Reserve University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008136","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Objective: Bacterial vaginosis is a dysbiosis of the vaginal microbiome, typically characterized by a loss of Lactobacillus. Lactobacillus plays a crucial role in vaginal immunity and protection against sexually transmitted infections. Herpes simplex virus 2, the primary cause of genital herpes, impacts 13% of people worldwide. We undertook this systematic review and meta-analysis to examine the risk of herpes simplex virus 2 acquisition in women with bacterial vaginosis. Secondarily, we examined the impact of bacterial vaginosis on herpes simplex virus 2 shedding, reactivation, and symptoms. Data sources: We searched PubMed, EMBASE, Cochrane, Web of Science, Google Scholar, and ClinicalTrials.gov for articles published before 1 July 2023 for microbiome and herpes simplex virus type 2. Studies were limited to human subjects and the English language. An updated search was performed in January 2026. This study was registered on PROSPERO (CRD42023439139). Methods of study selection: Studies on non-pregnant, reproductive-aged cisgender women that diagnosed bacterial vaginosis by Amsel Criteria, Nugent Scoring or used molecular techniques, and those that detected herpes simplex virus 2 by serological assay or PCR testing were included. Our search identified 863 results with four publications eligible for inclusion. For our secondary outcomes, 40 results were identified regarding herpes simplex virus 2 shedding, with two publications eligible for inclusion, which did not meet our threshold for meta-analysis. There were 21 results identified for herpes simplex virus 2 reaction and 115 results for herpes simplex virus 2 symptoms, with no articles being eligible for inclusion. Tabulation, integration, and results: Quality assessment was performed following data extraction using the quality assessment scales from the Joanna Briggs Institute. Results were extracted, and the pooled hazard ratio was calculated with 95% confidence interval. A total of 1906 women were included in this analysis, and 255 acquired herpes simplex virus 2. The pooled unadjusted hazard ratios produced an effect size of 1.91, (95% confidence interval 1.4649\u20132.4980), and a p-value of &lt;0.0001, while the pooled adjusted hazard ratios produces an effect size of 1.85, (95% confidence interval of 1.3556\u20132.5162), and a p-value of 0.0001 indicating that bacterial vaginosis is associated with a increased risk of herpes simplex virus 2 acquisition. Conclusions: This systematic review with meta-analysis indicates that bacterial vaginosis is associated with a significantly increased risk (91% unadjusted, 85% adjusted) of herpes simplex virus 2 acquisition, indicating that bacterial vaginosis treatment may reduce herpes simplex virus 2 acquisition. A notable limitation of these findings is the relatively small number of studies eligible for inclusion in this systematic review and meta-analysis.<\/jats:p>","DOI":"10.3390\/v18030330","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T11:06:52Z","timestamp":1773054412000},"page":"330","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Risk of HSV-2 Acquisition Among Women with Bacterial Vaginosis: Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"18","author":[{"given":"Taylor N.","family":"Whitt","sequence":"first","affiliation":[{"name":"Center for Global Health and Diseases, Department of Pathology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexis","family":"Heath","sequence":"additional","affiliation":[{"name":"Center for Global Health and Diseases, Department of Pathology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u2019Atra J.","family":"Hill","sequence":"additional","affiliation":[{"name":"Center for Global Health and Diseases, Department of Pathology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas K.","family":"Brubaker","sequence":"additional","affiliation":[{"name":"Center for Global Health and Diseases, Department of Pathology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA"},{"name":"Blood Heart Lung Immunology Research Center of University Hospitals and Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4165-6909","authenticated-orcid":false,"given":"Christina","family":"Farr Zuend","sequence":"additional","affiliation":[{"name":"Center for Global Health and Diseases, Department of Pathology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4680","DOI":"10.1073\/pnas.1002611107","article-title":"Vaginal microbiome of reproductive-age women","volume":"108","author":"Ravel","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","first-page":"4","article-title":"Bacterial vaginosis: A synthesis of the literature on etiology, prevalence, risk factors, and relationship with chlamydia and gonorrhea infections","volume":"3","author":"Bautista","year":"2016","journal-title":"Mil. Med. Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"O\u2019Hanlon, D.E., Moench, T.R., and Cone, R.A. (2013). Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080074"},{"key":"ref_4","first-page":"15","article-title":"Bacterial vaginosis: A practical review","volume":"30","author":"Bagnall","year":"2017","journal-title":"J. Am. Acad. Physician Assist."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ejogrb.2019.12.035","article-title":"Bacterial vaginosis\u2013A brief synopsis of the literature","volume":"245","author":"Coudray","year":"2020","journal-title":"Eur. J. Obs. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/0002-9343(83)91112-9","article-title":"Nonspecific vaginitis: Diagnostic criteria and microbial and epidemiologic associations","volume":"74","author":"Amsel","year":"1983","journal-title":"Am. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1128\/jcm.29.2.297-301.1991","article-title":"Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation","volume":"29","author":"Nugent","year":"1991","journal-title":"J. Clin. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1089\/aid.2018.0304","article-title":"The Evolving Facets of Bacterial Vaginosis: Implications for HIV Transmission","volume":"35","author":"McKinnon","year":"2019","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1097\/OLQ.0b013e318074e565","article-title":"The prevalence of bacterial vaginosis in the United States, 2001\u20132004; associations with symptoms, sexual behaviors, and reproductive health","volume":"34","author":"Koumans","year":"2007","journal-title":"Sex. Transm. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1007\/s00404-022-06817-5","article-title":"Effect of bacterial vaginosis on preterm birth: A meta-analysis","volume":"308","author":"Mohanty","year":"2023","journal-title":"Arch. Gynecol. Obs. Obstet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1097\/QAD.0b013e3283021a37","article-title":"Bacterial vaginosis and HIV acquisition: A meta-analysis of published studies","volume":"22","author":"Atashili","year":"2008","journal-title":"AIDS"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1086\/657320","article-title":"Bacterial vaginosis assessed by gram stain and diminished colonization resistance to incident gonococcal, chlamydial, and trichomonal genital infection","volume":"202","author":"Brotman","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gillet, E., Meys, J.F., Verstraelen, H., Bosire, C., De Sutter, P., Temmerman, M., and Broeck, D.V. (2011). Bacterial vaginosis is associated with uterine cervical human papillomavirus infection: A meta-analysis. BMC Infect. Dis., 11.","DOI":"10.1186\/1471-2334-11-10"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1086\/427777","article-title":"Effects of bacterial vaginosis and other genital infections on the natural history of human papillomavirus infection in HIV-1-infected and high-risk HIV-1-uninfected women","volume":"191","author":"Watts","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1136\/sti.2007.024794","article-title":"Association between bacterial vaginosis and Herpes simplex virus type-2 infection: Implications for HIV acquisition studies","volume":"83","author":"Nagot","year":"2007","journal-title":"Sex. Transm. Infect."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1093\/infdis\/jiv017","article-title":"Risk of Bacterial Vaginosis Among Women with Herpes Simplex Virus Type 2 Infection: A Systematic Review and Meta-analysis","volume":"212","author":"Esber","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Moola, S., Munn, Z., Tufanaru, C., Aromataris, E., Sears, K., Sfetcu, R., Currie, M., Qureshi, R., Mattis, P., and Lisy, K. (2020). Chapter 7: Systematic reviews of etiology and risk. JBI Manual for Evidence Synthesis, JBI.","DOI":"10.46658\/JBIRM-17-06"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1136\/sti.2009.036103","article-title":"A prospective study of risk factors for herpes simplex virus type 2 acquisition among high-risk HIV-1 seronegative women in Kenya","volume":"85","author":"Chohan","year":"2009","journal-title":"Sex. Transm. Infect."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1086\/375819","article-title":"Association between acquisition of herpes simplex virus type 2 in women and bacterial vaginosis","volume":"37","author":"Cherpes","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1097\/OLQ.0b013e31816fcaf8","article-title":"Risk factors for incident herpes simplex type 2 virus infection among women attending a sexually transmitted disease clinic","volume":"35","author":"Gallo","year":"2008","journal-title":"Sex. Transm. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1086\/423323","article-title":"Incidence of herpes simplex virus type 2 infection in 5 sexually transmitted disease (STD) clinics and the effect of HIV\/STD risk-reduction counseling","volume":"190","author":"Gottlieb","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1136\/sti.2008.035543","article-title":"Bacterial vaginosis in female facility workers in north-western Tanzania: Prevalence and risk factors","volume":"85","author":"Baisley","year":"2009","journal-title":"Sex. Transm. Infect."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1086\/429622","article-title":"Genital tract shedding of herpes simplex virus type 2 in women: Effects of hormonal contraception, bacterial vaginosis, and vaginal group B Streptococcus colonization","volume":"40","author":"Cherpes","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Rahman, N., Mian, M.F., Hayes, C.L., Nazli, A., and Kaushic, C.G. (2024). vaginalis increases HSV-2 infection by decreasing vaginal barrier integrity and increasing inflammation in vivo. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1487726"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e70152","DOI":"10.1002\/jev2.70152","article-title":"Extracellular Vesicles Containing MDP Derived from Lactobacillus rhamnosus GG Inhibit HSV-2 Infection by Activating the NOD2-IFN-I Signalling Pathway","volume":"14","author":"Wang","year":"2025","journal-title":"J. Extracell. Vesicles"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Avitabile, E., Menotti, L., Giordani, B., Croatti, V., Parolin, C., and Vitali, B. (2024). Vaginal Lactobacilli Supernatants Protect from Herpes Simplex Virus Type 1 Infection in Cell Culture Models. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052492"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/3\/330\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T05:21:57Z","timestamp":1773120117000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/3\/330"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,7]]},"references-count":27,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["v18030330"],"URL":"https:\/\/doi.org\/10.3390\/v18030330","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,7]]}}}