Herpes simplex virus type 2 antibody detection performance in Kisumu, Kenya, using the Herpeselect ELISA, Kalon ELISA, Western blot and inhibition testing

Smith, Jennifer S.; Bailey, Robert C.; Westreich, Daniel; Maclean, Ian; Agot, Kawango; Ndinya‐Achola, Jeckoniah; Hogrefe, Wayne; Morrow, Rhoda Ashley; Moses, Stephen

doi:10.1136/sti.2008.031815

Cited by 36 publications

(41 citation statements)

References 14 publications

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“…If HIV-1-infected workers were less likely to participate in the study, this would have led us to underestimate the true HIV-1 prevalence at baseline. Additionally, tests for HSV-2 lack specificity13 when the manufacturer's suggested cut-off is used, and further testing with a western blot ‘gold standard’ could not be performed. To combat this, we repeated our multivariate analysis using a higher cut-off to increase test specificity, and our results were not substantially changed.…”

Section: Discussionmentioning

confidence: 99%

High prevalent and incident HIV-1 and herpes simplex virus 2 infection among male migrant and non-migrant sugar farm workers in Zambia

Heffron

Chao

Mwinga

et al. 2011

Sexually Transmitted Infections

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BackgroundMore insight is needed regarding risk factors for prevalent and incident HIV-1 infection among male farm workers in Sub-Saharan Africa to control the HIV-1 epidemic.MethodsMale farm workers were recruited from a sugar estate in Zambia to participate in a prospective cohort study. Questionnaire data were collected via interview, and testing was conducted for HIV-1, herpes simplex virus type 2 (HSV-2), and syphilis infection at baseline and follow-up between May 2006 and September 2007.ResultsAmong 1062 workers enrolled, HIV-1 prevalence at baseline was 20.7%. Testing HSV-2 seropositive (adjusted odds ratio (AOR) 5.4, 95% CI 3.6 to 8.1), self-reported genital ulcers in the past year (AOR 2.8, 95% CI 1.9 to 4.2), and being widowed (AOR 3.7, 95% CI 2.0 to 6.9) were significantly associated with prevalent HIV-1 infection. The HIV-1 incidence among 731 initially negative participants with at least one follow-up visit was 4.1 per 1000 person-months (95% CI 2.6 to 5.7); seroconversion was independently associated with prevalent HSV-2 infection (adjusted hazard ratio (AHR) 2.4, 95% CI 1.0 to 5.8) and incident HSV-2 infection (AHR 18.0, 95% CI 4.2 to 76.3). HIV-1 prevalence and incidence rates were similar among migrant and non-migrant workers.ConclusionsHIV-1 prevalence and incidence were high, and HSV-2 infection was a risk factor for HIV-1 acquisition. There is an urgent need to expand HIV-1 prevention programmes tailored to farm workers and their communities.

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Section: Discussionmentioning

confidence: 99%

High prevalent and incident HIV-1 and herpes simplex virus 2 infection among male migrant and non-migrant sugar farm workers in Zambia

Heffron

Chao

Mwinga

et al. 2011

Sexually Transmitted Infections

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“…Positively selected amino acid residues were frequently identi- fied in HSV glycoproteins, with the highest number of positively selected sites occurring in gC-1 and gG-2. This finding, along with the detection of five or more positively selected sites in gG-2 and a high number of nonsynonymous substitutions, was an indication that perhaps nucleotide variation and the resulting antigenic variation were impacting the sensitivity or specificity of the Western blot assay in East Africa, where there is a significant difference between ELISA and Western blot results (25)(26)(27)(28). This may be due in part to the U.S. strain of HSV-2 used to provide the antigens in the Western blot and extends to the antigen used in commercial ELISAs.…”

Section: Discussionmentioning

confidence: 99%

“…Because serology tests used to discriminate HSV-1 and HSV-2 infections are frequently inaccurate in East African populations (25)(26)(27)(28), we further examined HSV-2 gG amino acid sequences using phylogenetic methods. The analysis demonstrated that most global strains were dispersed around the tree, with few clusters with bootstrap support greater than 50%; however, there was one large (14 sequences), low-diversity clade (Ͻ0.1%) with moderate bootstrap support (Ͼ60%) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Importantly, HSV glycoproteins, in particular gG, are the target of antibody detection assays used for the diagnosis of HSV-1 or HSV-2 infections (23); therefore, a comparison of HSV-1 and HSV-2 glycoproteins could show why these tests sometimes fail, especially in East Africa, where some serological tests have an assay specificity as low as 50.7% (24)(25)(26)(27)(28). We analyzed all putative glycoprotein genes in the U L and U S regions, which included sequences derived from North America, Europe, Asia, the Republic of South Africa, and East Africa.…”

mentioning

confidence: 99%

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Global Diversity within and between Human Herpesvirus 1 and 2 Glycoproteins

Lamers¹,

Newman

Laeyendecker

et al. 2015

J Virol

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Human herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) are large-genome DNA viruses that establish a persistent infection in sensory neurons and commonly manifest with recurring oral or genital erosions that transmit virus. HSV encodes 12 predicted glycoproteins that serve various functions, including cellular attachment, entry, and egress. Glycoprotein G is currently the target of an antibody test to differentiate HSV-1 from HSV-2; however, this test has shown reduced capacity to differentiate HSV strains in East Africa. Until the recent availability of 26 full-length HSV-1 and 36 full-length HSV-2 sequences, minimal comparative information was available for these viruses. In this study, we use a variety of sequence analysis methods to compare all available sequence data for HSV-1 and HSV-2 glycoproteins, using viruses isolated in Europe, Asia, North America, the Republic of South Africa, and East Africa. We found numerous differences in diversity, nonsynonymous/synonymous substitution rates, and recombination rates between HSV-1 glycoproteins and their HSV-2 counterparts. Phylogenetic analysis revealed that while most global HSV-2 glycoprotein G sequences did not form clusters within or between continents, one clade (supported at 60.5%) contained 37% of the African sequences analyzed. Accordingly, sequences from this African subset contained unique amino acid signatures, not only in glycoprotein G, but also in glycoproteins I and E, which may account for the failure of sensitive antibody tests to distinguish HSV-1 from HSV-2 in some African individuals. Consensus sequences generated in the study can be used to improve diagnostic assays that differentiate HSV-1 from HSV-2 in global populations. IMPORTANCEHuman herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) are large DNA viruses associated with recurring oral or genital erosions that transmit virus. Up to 12 HSV-1 and HSV-2 glycoproteins are involved in HSV cell entry or are required for viral spread in animals, albeit some are dispensable for replication in vitro. The recent availability of comparable numbers of full-length HSV-1 and HSV-2 sequences enabled comparative analysis of gene diversity of glycoproteins within and between HSV types. Overall, we found less glycoprotein sequence diversity within HSV-2 than within the HSV-1 strains studied, while at the same time, several HSV-2 glycoproteins were evolving under less selective pressure. Because HSV glycoproteins are the focus of antibody tests to detect and differentiate between infections with the two strains and are constituents of vaccines in clinical-stage development, these findings will aid in refining the targets for diagnostic tests and vaccines. H erpes simplex virus 1 and 2 (HSV-1 and HSV-2) are members of the subfamily Alphaherpesvirinae. They are large, enveloped DNA viruses that cause infections that cycle between a replication stage, where infectious virus particles are shed through mucocutaneous erosions, and a latent infection stage, where the virus persists in sensory neurons (1)...

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“…Currently, when using the Focus HSV-2 ELISA in a low-risk or heterogeneous setting, the index value for interpreting positivity should be raised from .1.1 to !3.5 (IIa, B), taking into account that this reduces sensitivity for both early and established infection. 29,30,33 Samples with values between 1.1 and 3.5 should undergo confirmation by an alternative method (e.g. Biokit HSV-2 or Kalon ELISA) (IIa, B).…”

Section: Transmission Riskmentioning

confidence: 99%