Trends in Herpes Simples Virus Type 2 infection in the United States Fujie Xu, Geraldine McQuillan, Benny Kottiri, Maya Sternberg, Francis Lee, André Nahmias,

Trends in Herpes Simples Trends in Herpes Simples Virus Type 2 infection in Virus Type 2 infection in

the United Statesthe United States Fujie Xu, Geraldine McQuillan, Benny Kottiri, Fujie Xu, Geraldine McQuillan, Benny Kottiri, Maya Sternberg, Francis Lee, AndrMaya Sternberg, Francis Lee, Andréé Nahmias, Nahmias,

Lauri MarkowitzLauri Markowitz

Centers for Disease Control and Prevention (CDC) Centers for Disease Control and Prevention (CDC) Emory UniversityEmory University

BackgroundBackgroundHSV-2 is the cause of most genital herpesHSV-2 is the cause of most genital herpes

HSV-2 increases the risk for HIV acquisition HSV-2 increases the risk for HIV acquisition and transmissionand transmission

HSV-2 seroprevalence is a marker of sexual HSV-2 seroprevalence is a marker of sexual risk behaviorsrisk behaviors

In adolescents and young adults, HSV-2 In adolescents and young adults, HSV-2 seroprevalence is a measure of seroprevalence is a measure of moremore recentrecent risky sexual behaviorsrisky sexual behaviors

Data SourceData Source

NHANESNHANES——NNational ational HHealth ealth AAnd nd NNutrition utrition EExamination xamination SSurveyurvey

A series of nationally representative surveys A series of nationally representative surveys of non-institutionalized US populationof non-institutionalized US population

Survey staff travel across the nation to Survey staff travel across the nation to conduct interviews and health examinations conduct interviews and health examinations

Study ObjectivesStudy Objectives

Describe trends of HSV-2 seroprevalence Describe trends of HSV-2 seroprevalence in the US between two NHANES surveys:in the US between two NHANES surveys:

NHANES III: 1988-1994NHANES III: 1988-1994

NHANES 1999-2000NHANES 1999-2000

The mid-point interval between this two The mid-point interval between this two surveys was 8.5 yearssurveys was 8.5 years

Statistical MethodsStatistical Methods

Age-adjustment Age-adjustment – 2000 US Census as the standard population2000 US Census as the standard population

WeightsWeights– Accounting for oversampling and non-Accounting for oversampling and non-

responseresponse

SUDAAN software SUDAAN software – Accounting for multi-stage sampling designAccounting for multi-stage sampling design

HSV-2 SerologyHSV-2 Serology

Type-specific immunodot assay Type-specific immunodot assay – Glycoprotein of gG2 as antigenGlycoprotein of gG2 as antigen

The same assay and the same laboratory was The same assay and the same laboratory was used for both surveysused for both surveys

ResultsResultsSurveysSurveys NHANES III NHANES III

(1988-1994) (1988-1994) NHANES NHANES

1999-2000 1999-2000

Examination rateExamination rate 76%76% 78%78%

Sample sizeSample size

TotalTotal

By age (years)By age (years)

14-19 14-19

20-2920-29

30-3930-39

40-4940-49

91659165

17871787

27502750

25672567

20612061

35903590

15151515

717717

708708

650650

Changes in Changes in HSV-2 HSV-2 SeroprevalenceSeroprevalenceBy Age GroupBy Age Group

VariablesVariables NHANES III NHANES III

(1988-1994) (1988-1994)

% (95% CI)% (95% CI)

NHANES NHANES

1999-2000 1999-2000

% (95% CI)% (95% CI)

PercentagePercentage

changechange

Total Total

Age (yrs)Age (yrs)

14-1914-19

20-2920-29

30-3930-39

40-4940-49

21.3 (19.4, 23.3) 21.3 (19.4, 23.3)

5.8 (4.4, 7.5 )5.8 (4.4, 7.5 )

17.2 (14.9, 19.8)17.2 (14.9, 19.8)

27.8 (24.6, 31.4)27.8 (24.6, 31.4)

26.3 (23.0, 30.1)26.3 (23.0, 30.1)

17.6 (15.4, 20.0)17.6 (15.4, 20.0)

1.5 (0.9, 2.7)1.5 (0.9, 2.7)

8.9 (7.2, 11.1)8.9 (7.2, 11.1)

25.4 (21.6, 29.9)25.4 (21.6, 29.9)

26.4 (21.4, 32.5)26.4 (21.4, 32.5)

-17%†-17%†

-74%‡-74%‡

-48%‡-48%‡

-9%-9%

-0%-0%CI, confidence interval. † p<0.05; ‡ p<0.001

Changes in Changes in HSV-2 HSV-2 SeroprevalenceSeroprevalenceBy Age GroupBy Age Group

0

10

20

30

40

50

14-19 20-29 30-39 40-49

Age Groups (Years)

HS

V-2

Ser

op

reva

len

ce (

%)

NHANES III

NHANES '99-00

Changes in Changes in HSV-2HSV-2 Seroprevalence Seroprevalence

VariablesVariables NHANES III NHANES III (1988-1994) (1988-1994)

% (95% CI)% (95% CI)

NHANES NHANES

1999-2000 1999-2000

% (95% CI)% (95% CI)

PercentagePercentage

changechange

SexSex

Males Males

FemalesFemales

Race/ethnicityRace/ethnicity

NH whitesNH whites

NH blacksNH blacks

Mex AmericansMex Americans

17.2 (14.8, 19.9)17.2 (14.8, 19.9)

25.4 (23.5, 27.5)25.4 (23.5, 27.5)

16.7 (14.6, 19.1)16.7 (14.6, 19.1)

43.0 (40.9, 45.143.0 (40.9, 45.1

22.5 (20.4, 24.8)22.5 (20.4, 24.8)

11.2 (9.1, 13.8)11.2 (9.1, 13.8)

23.5 (20.5, 27.1)23.5 (20.5, 27.1)

13.5 (10.8, 16.8) 13.5 (10.8, 16.8)

40.3 (36.4, 44.7) 40.3 (36.4, 44.7)

12.1 (9.5, 15.5) 12.1 (9.5, 15.5)

-35%†-35%†

-7%-7%

-19%-19%

-6%-6%

-46%‡-46%‡

CI, confidence interval. † p<0.05; ‡ p<0.001

Changes in HSV-2 Seroprevalence Changes in HSV-2 Seroprevalence in in 14-29 year-olds14-29 year-olds

VariablesVariables NHANES III NHANES III (1988-1994) (1988-1994)

N = 4537N = 4537

% (95% CI)% (95% CI)

NHANES NHANES

1999-2000 1999-2000

N = 2232N = 2232

% (95% CI)% (95% CI)

PercentagePercentage

changechange

SexSex

Males Males

FemalesFemales

Race/ethnicityRace/ethnicity

NH whitesNH whites

NH blacksNH blacks

Mex AmericansMex Americans

9.8 (7.5, 12.9)9.8 (7.5, 12.9)

16.6 (14.9, 18.6)16.6 (14.9, 18.6)

11.1 (9.0, 13.9)11.1 (9.0, 13.9)

24.9 (21.9, 28.2)24.9 (21.9, 28.2)

11.7 (9.7, 14.1)11.7 (9.7, 14.1)

4.0 (2.7, 5.9)4.0 (2.7, 5.9)

8.5 (6.4, 11.2)8.5 (6.4, 11.2)

3.3 (1.9, 5.4) 3.3 (1.9, 5.4)

21.9 (16.8, 28.5) 21.9 (16.8, 28.5)

6.2 (3.6, 10.8) 6.2 (3.6, 10.8)

-59%‡-59%‡

-49%‡-49%‡

-70%†-70%†

-12%-12%

-47%†-47%†

CI, confidence interval. † p<0.05; ‡ p<0.001

ConclusionsConclusions

HSV-2 seroprevalence decreased HSV-2 seroprevalence decreased significantly between NHANES III and significantly between NHANES III and NHANES ‘99-00NHANES ‘99-00The largest decrease occurred in The largest decrease occurred in adolescentsadolescentsIn adolescents and young adults (14-29 In adolescents and young adults (14-29 year-olds), significant decreases occurred year-olds), significant decreases occurred in all sex and race/ethnicity groups except in all sex and race/ethnicity groups except non-Hispanic blacksnon-Hispanic blacks

LimitationsLimitations

Limited behavioral data in NHANESLimited behavioral data in NHANES– The number of lifetime sex partnersThe number of lifetime sex partners

– Changes in methods and wordingsChanges in methods and wordings

Changes in US populationChanges in US population– Mexican AmericansMexican Americans

Small sample size of NHANES’99-00Small sample size of NHANES’99-00

DiscussionDiscussion

Is the decrease in HSV-2 infection real?Is the decrease in HSV-2 infection real?

NHANES 2001-2002 to be released in NHANES 2001-2002 to be released in May 2004May 2004

HSV-2 included in NHANES 2003-2004HSV-2 included in NHANES 2003-2004

Changes in HSV-2 Seroprevalence Changes in HSV-2 Seroprevalence between NHANES II and NHANES IIIbetween NHANES II and NHANES III

0

10

20

30

40

50

14-19 20-29 30-39 40-49

Age Groups (Years)

HS

V-2

Sero

pre

vale

nce (

%)

NHANES II

NHANES III

Fleming DT et al. N Engl J Med 1997; 337: 1105-11.

HSV-2 Seroprevalence in NHANES HSV-2 Seroprevalence in NHANES By Age GroupBy Age Group

0

10

20

30

40

50

14-19 20-29 30-39 40-49

Age Groups (Years)

HS

V-2

Ser

op

reva

len

ce (

%)

NHANES II

NHANES III

NHANES '99-00

Discussion (cont)Discussion (cont)

Youth Risk Behavior Surveys (1991-2001)*Youth Risk Behavior Surveys (1991-2001)* Ever had sexEver had sex

Had four or more partnersHad four or more partners

Used condomsUsed condoms

Between 1990 and 2000, teen pregnancy rates in Between 1990 and 2000, teen pregnancy rates in women aged 15-19 in the US decreased 28%**.women aged 15-19 in the US decreased 28%**.

* CDC. MMWR 2002; 51:856-859. **Data from the Alan Guttmacher InstituteData from the Alan Guttmacher Institute

Teenage Pregnancy Rate Teenage Pregnancy Rate in the US, 1972-2000in the US, 1972-2000

80

90

100

110

120

1970 1975 1980 1985 1990 1995 2000

Year

Rate per 1,000 women aged 15-19

Changes in Changes in HSV-1HSV-1 Seroprevalence Seroprevalence between the two NHANES Surveysbetween the two NHANES Surveys

VariablesVariables NHANES III NHANES III (1988-1994) (1988-1994)

% (95% CI)% (95% CI)

NHANES NHANES

1999-2000 1999-2000

% (95% CI)% (95% CI)

PercentagePercentage

changechange

Total Total

By ageBy age

14-1914-19

20-2920-29

30-3930-39

40-4940-49

62 (59, 65) 62 (59, 65)

46 (42, 50)46 (42, 50)

56 (52, 60)56 (52, 60)

66 (62, 70)66 (62, 70)

73 (69, 77)73 (69, 77)

60 (57, 62)60 (57, 62)

43 (38, 49)43 (38, 49)

59 (55, 63)59 (55, 63)

64 (60, 68)64 (60, 68)

65 (60, 70)65 (60, 70)

-4%-4%

-5%-5%

5%5%

-2%-2%

-11%†-11%†

CI, confidence interval. † p<0.05

Discussion (cont)Discussion (cont)

An analysis found that about 25% of the An analysis found that about 25% of the decline in teenage pregnancy between 1988 decline in teenage pregnancy between 1988 and 1995 was due to decreased sexual activity.and 1995 was due to decreased sexual activity.

* Data from the Alan Guttmacher Institute* Data from the Alan Guttmacher Institute