Negative epidemiological association between HSV-1 and HSV-2 infections

Objectives: Existing evidence on an epidemiological association between herpes simplex virus (HSV) type 1 and type 2 infections remains conflicting and inconclusive. Using a multi-national database of HSV-1/2 serological testing, we aimed to assess the existence of an association between both infections. Design, Setting, and Participants: An HSV-1/2 cross-sectional serological testing database was assembled by merging databases of seroprevalence studies on men blood donors residing currently in Qatar, but from different countries. Specimens were tested for anti-HSV-1 IgG antibodies using HerpeSelect (R) 1 ELISA, and for anti-HSV-2 IgG anti-bodies following a two-test algorithm: HerpeSelect (R) 2 ELISA to test the sera, and Euroline-WB to confirm positive and equivocal specimens. Logistic regressions were conducted to estimate unadjusted and adjusted infection odds ratios. Results: Serological testing for HSV-1/2 was performed on 2522 specimens. Sero-positivity for HSV-1 and HSV-2 was identified in 2053 (81.5%) and 87 (3.5%) specimens, respectively. Univariable analyses estimated higher odds of HSV-2 infection with increasing age and increasing country income level, and an unadjusted odds ratio with HSV-1 sero-positivity of 0.71 (95% CI 0.43-1.17; p-value 0.172). Adjusting for age and country income level, the adjusted odds ratio of HSV-2 infection with HSV-1 sero-positivity was 0.51 (95% CI 0.30-0.87; p-value 0.013). Sensitivity analyses confirmed this association. Conclusions: There is a negative association between HSV-1 and HSV-2 infections, suggestive of a protective effect for HSV-1 sero-positivity against HSV-2 acquisition. This finding supports earlier pooled but inconclusive evidence from prospective studies, yet contrasts with pooled findings of earlier cross-sectional studies.