Table of Contents

Component Description

Herpes Simplex Virus (HSV) is categorized by two types: HSV-1 and HSV-2. HSV-1 is a common chronic infection that is the cause of most oral herpes or cold sores. HSV-2 is a sexually transmitted infection and can be used as a marker for sexual transmission of other infectious agents. HSV-2 infections are rarely life threatening, but morbidity due to painful genital ulcerations is significant (CDC, 2024).

HSV-2 infection is one of the best markers of sexual risk factors leading to sexually transmitted infections, because: (a) HSV-2 infections are common and, thus, HSV-2 rates are a measure of sexual risk in the broader population beyond high risk groups; (b) HSV-2 infection is almost always a result of sexual transmission and, thus, a specific measure of sexually transmitted infection; (c) HSV-2 infections are not curable and, thus, HSV-2 risk is not influenced by health care-seeking factors; and (d) sensitive, specific, and relatively inexpensive tests for HSV-2 antibody are available. HSV-2 is a very important marker for monitoring the impact of large national efforts, motivated by the HIV epidemic, to reduce risky sexual behaviors.

NHANES laboratory data can be linked to NHANES sexual behavior questions to assist in the understanding of national trends in HIV and sexually transmitted infections (STIs). The availability of STI and risk factor data in a national sample over time is a unique and invaluable resource for evaluation of national HIV/STI risk-reduction efforts and for risk-based modeling of the burden and trends of STIs.

Eligible Sample

Examined participants aged 14–49 years were eligible. This data file only includes examined participants aged 14-49 years for HSV-1 and 18-49 years for HSV-2 with limited access. HSV-2 data from participants aged 14–17 years are available in a separate dataset: Herpes Simplex Virus Type-2– Youth (HSV_L_R). Both datasets may be accessed through the NCHS Research Data Center.

Description of Laboratory Methodology

Although extensive antigenic cross-reactivity exists between the two viral types of herpes, a viral glycoprotein specific for HSV-2 (designated gG-2) and a glycoprotein specific for HSV-1 (designated gG-1) have been identified. Monoclonal antibodies and affinity chromatography have been used to purify these glycoproteins and thus provide antigens for type-specific herpes serologic assays. Solid-phase enzymatic immunodot assays are used to detect antibodies reactive to these antigens. The purified glycoprotein, gG-1 or gG-2, is adsorbed to the center of a nitrocellulose disk. The rest of the disk surface is coated with bovine serum albumin to prevent further nonspecific protein adsorption. Incubation of test serum with the disk allows specific antibodies, if present, to bind to the immobilized antigen. After extensive washing to remove non-reactive antibodies, the bound antibodies are detected by sequential treatment with peroxidase-conjugated goat-anti-human IgG and the enzyme substrate (H2O2 with chromogen 4-chloro-1-naphthol). A positive reaction is demonstrated by the appearance of a blue dot at the center of the disk. Serum reactive to an immunodot charged with gG-1 indicates the person being tested has HSV-1 infection. Serum reactive to an immunodot charged with gG-2 indicates the person being tested has HSV-2 infection.

Refer to the Laboratory Method Files section for a detailed description of the laboratory methods used.

There were no changes to the lab method, lab equipment, or lab site in the NHANES August 2021-August 2023 cycle.

Laboratory Method Files

Herpes Simplex Virus Type 1 & 2 (May 2025)

Laboratory Quality Assurance and Monitoring

Serum specimens were processed, stored, and shipped to Emory University, Atlanta, GA for analysis.

Detailed instructions on specimen collection and processing are discussed in the NHANES Laboratory Procedures Manual (LPM). Vials are stored under appropriate frozen (–30°C) conditions until they are shipped to Emory University for testing.

The NHANES quality assurance and quality control (QA/QC) protocols meet the 1988 Clinical Laboratory Improvement Amendment mandates. Detailed QA/QC instructions are discussed in the NHANES LPM.

Mobile Examination Centers (MECs)

Laboratory team performance is monitored using several techniques. NCHS and contract consultants use a structured competency assessment evaluation during visits to evaluate both the quality of the laboratory work and the QC procedures. Each laboratory staff member is observed for equipment operation, specimen collection and preparation; testing procedures and constructive feedback are given to each staff member. Formal retraining sessions are conducted annually to ensure that required skill levels were maintained.

Analytical Laboratories

NHANES uses several methods to monitor the quality of the analyses performed by the contract laboratories. In the MEC, these methods include performing blind split samples collected on “dry run” sessions. In addition, contract laboratories randomly perform repeat testing on 2% of all specimens.

NCHS developed and distributed a QC protocol for all CDC and contract laboratories, which outlined the use of Westgard rules (Westgard, et. al. 1981) when testing NHANES specimens. Progress reports containing any problems encountered during shipping or receipt of specimens, summary statistics for each control pool, QC graphs, instrument calibration, reagents, and any special considerations are submitted to NCHS quarterly. The reports are reviewed for trends or shifts in the data. The laboratories are required to explain any identified areas of concern.  

Data Processing and Editing

The data were reviewed. Incomplete data or improbable values were sent to the performing laboratory for confirmation.

Analytic Notes

There are over 800 laboratory tests performed on NHANES participants. However, not all participants provided biospecimens or enough volume for all the tests to be performed. The specimen availability can also vary by age or other population characteristics. Analysts should evaluate the extent of missing data in the dataset related to the outcome of interest as well as any predictor variables used in the analyses to determine whether additional re-weighting for item non-response is necessary.

Please refer to the NHANES Analytic Guidelines and the on-line NHANES Tutorial for details on the use of sample weights and analytic issues.

Phlebotomy Weights

For the August 2021-August 2023 cycle, analysis of nonresponse patterns for the phlebotomy component in the MEC examination revealed differences by age group and race/ethnicity, among other characteristics. For example, approximately 67% of children aged 1-17 years who were examined in the MEC provided a blood specimen through phlebotomy, while 95% of examined adults aged 18 and older provided a blood specimen. Therefore, an additional phlebotomy weight, WTPH2YR, has been included in this data release to address possible nonresponse bias. Participants who are eligible but did not provide a blood specimen have their phlebotomy weight assigned a value of “0” in their records. The phlebotomy weight should be used for analyses that use variables derived from blood analytes, and is included in all relevant data files.

Demographic and Other Related Variables

The analysis of NHANES laboratory data must be conducted using the appropriate survey design and demographic variables. The NHANES August 2021-August 2023 Demographics File contains demographic data, health indicators, and other related information collected during household interviews as well as the sample design variables. The recommended procedure for variance estimation requires use of stratum and PSU variables (SDMVSTRA and SDMVPSU, respectively) in the demographic data file.

The Fasting Questionnaire File includes auxiliary information, such as fasting status, length of fast and the time of venipuncture.

This laboratory data file can be linked to the other NHANES data files using the unique survey participant identifier (i.e., SEQN).

The items LBXHE1 and LBXHE2 represent type-specific enzymatic immunodot assay results. The type-specific immunodot assays used to detect antibodies reactive to HSV-1 and HSV-2 antigens in NHANES August 2021-August 2023 cycle are the same assays as those used in NHANES 1999–2016 cycles and NHANES III. Therefore, HSV-1 and HSV-2 results from these surveys are comparable for trend analyses.

Detection Limits

Since this data is reported as qualitative data the use of lower limits of detection (LLODs) is not applicable.

References

Codebook and Frequencies

SEQN - Respondent sequence number

Variable Name:
SEQN
SAS Label:
Respondent sequence number
English Text:
Respondent sequence number
Target:
Both males and females 14 YEARS - 49 YEARS

WTPH2YR - Phlebotomy 2 Year Weight

Variable Name:
WTPH2YR
SAS Label:
Phlebotomy 2 Year Weight
English Text:
Phlebotomy 2 Year Weight
Target:
Both males and females 14 YEARS - 49 YEARS
Code or Value Value Description Count Cumulative Skip to Item
6213.3002375 to 241728.85724 Range of Values 2948 2948
0 No blood sample provided 241 3189
. Missing 0 3189

LBXHE1 - Herpes Simplex Virus Type 1

Variable Name:
LBXHE1
SAS Label:
Herpes Simplex Virus Type 1
English Text:
Herpes Simplex Virus Type 1
Target:
Both males and females 14 YEARS - 49 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Positive 1122 1122
2 Negative 1601 2723
3 Indeterminate 4 2727
. Missing 462 3189

LBXHE2 - Herpes Simplex Virus Type 2

Variable Name:
LBXHE2
SAS Label:
Herpes Simplex Virus Type 2
English Text:
Herpes Simplex Virus Type 2
Target:
Both males and females 18 YEARS - 49 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Positive 310 310
2 Negative 1967 2277
3 Indeterminate 9 2286
. Missing 903 3189