Untreated Gonococcal and Chlamydial Infection in a Probability Sample of
Adults
JAMA. 2002;287:726-733
Author Information <http://jama.ama-assn.org/issues/v287n6/rfull/#aainfo>
Charles F. Turner, PhD; Susan M. Rogers, PhD; Heather G. Miller, PhD;
William C. Miller, MD, PhD; James N. Gribble, ScD; James R. Chromy, PhD;
Peter A. Leone, MD; Phillip C. Cooley, MS; Thomas C. Quinn, MD; Jonathan M.
Zenilman, MD
Context The prevalence and distribution of gonococcal and chlamydial
infections in the general population are poorly understood. Development of
nucleic acid amplification tests, such as the ligase chain reaction assay,
provides new opportunities to estimate the prevalence of untreated
infections in the population.
Objective To estimate the overall prevalence of untreated gonococcal and
chlamydial infections and to describe patterns of infection within specific
demographic subgroups of the young adult population in Baltimore, Md.
Design and Setting Cross-sectional behavioral survey based on a probability
sample of Baltimore households with collection of urine specimens between
January 1997 and September 1998.
Participants A total of 728 adults aged 18 to 35 years completed the
interview portion of the study, and 579 of these respondents also provided a
urine specimen adequate for testing.
Main Outcome Measure Prevalence of untreated infection, as measured by the
percentage of specimens testing positive for gonococcal and chlamydial
infection by ligase chain reaction, weighted to reflect variations in
probabilities of sample selection from the population. Alternate estimates
of the prevalence of recent treated infection were derived from clinically
diagnosed cases reported to the Baltimore City Health Department and by
diagnoses reported by participants in the survey.
Results An estimated 5.3% (SE, 1.4%) of the population aged 18 to 35 years
has an untreated gonococcal infection, and 3.0% (SE, 0.8%) is estimated to
have an untreated chlamydial infection. While 7.9% (SE, 1.6%) of the
population is estimated to have either an untreated gonococcal or chlamydial
infection, estimated prevalence is substantially higher among black women
(15.0%; SE, 3.7%). Few participants with untreated infections reported
dysuria or discharge during the 6 months preceding testing. The estimated
number of untreated gonococcal infections in the population (9241; SE, 2441)
substantially exceeds both the number of such infections diagnosed among
Baltimore adults aged 18 to 35 years and reported to the Baltimore City
Health Department during 1998 (4566), and the estimated number of diagnoses
derived using participants' reports for the 12 months prior to the survey
(4708 [SE, 1918] to 5231 [SE, 2092]). The estimated number of untreated
chlamydial infections (5231; SE, 1395) is also greater than the number of
cases reported to the health department in 1998 (3664) but is slightly less
than the estimated number of diagnoses derived using participants' reports
of chlamydial infections diagnosed during the 12 months prior to the survey
(5580 [SE, 1918] to 6975 [SE, 2441]).
Conclusion In 1997-1998, the estimated number of undiagnosed gonococcal and
chlamydial infections prevalent in the population of Baltimore adults aged
18 to 35 years approached or exceeded the number of infections that were
diagnosed and treated annually.
JAMA. 2002;287:726-733
JOC10483
Untreated infection with Neisseria gonorrhoeae or Chlamydia trachomatis can
result in chronic pelvic pain, infertility, and potentially fatal ectopic
pregnancies among women. In addition, these bacterial sexually transmitted
diseases (STDs) serve as biological cofactors that facilitate transmission
of human immunodeficiency virus (HIV). Untreated chlamydial infections, for
example, are estimated to increase the likelihood of HIV transmission by a
factor of 1.4 to 3.3. 1-3 <http://jama.ama-assn.org/issues/v287n6/rfull/#r1>
Unfortunately, the prevalence and distribution of these STDs within the
population are poorly understood. Until recently, our knowledge was limited
by its exclusive dependence on 2 data sources with well-recognized
inadequaciesthe counting of infections reported to public health departments
and studies of convenience samples of special populations, such as clinic
patients. While these sources can provide useful information, they are
inherently incapable of characterizing untreated STD infection in the
population at large. This problem is particularly severe for infections
whose symptoms are mild or nonexistent. Available evidence suggests that a
substantial fraction of gonococcal and chlamydial infections are
asymptomatic. 4-8 <http://jama.ama-assn.org/issues/v287n6/rfull/#r4> The
Institute of Medicine has noted, 8
<http://jama.ama-assn.org/issues/v287n6/rfull/#r8> such STDs spawn " . . .
hidden epidemics of tremendous health and economic consequence in the United
States . . . [T]he scope, impact, and consequences of [these] STDs are
underrecognized by the public and health care professionals."
The recent development of nucleic acid amplification tests (NAATs) for the
diagnosis of gonococcal and chlamydial infections using urine specimens has
generated new models for research on the epidemiology of these STDs. 9-11
<http://jama.ama-assn.org/issues/v287n6/rfull/#r9> Since the urine
specimens required for NAAT can be obtained in population surveys,
generalizations about the prevalence and patterns of infection now can be
derived from surveys of probability samples of the general population rather
than samples of clinic patients or other special populations. This research
model provides estimates (with known margins of sampling error) for the
prevalence of untreated infections both in the population at large and in
identifiable subpopulations.
To provide a more accurate understanding of the hidden epidemics of
untreated infection with N gonorrhoeae and C trachomatis, using probability
sampling methods, we recruited a population sample of young adults aged 18
to 45 years to participate in a survey of sexual and other sensitive
behaviors and STD history. We then used NAATs of urine specimens obtained
from survey respondents aged 18 to 35 years to detect the presence of
untreated gonococcal and chlamydial infections. The resultant data allowed
us to estimate the prevalence and patterns of untreated infection in our
target population, adults aged 18 to 35 years in Baltimore, Md.
METHODS
Sample Design
The sample for the Baltimore STD and Behavior Survey was drawn from
households residing within the municipal boundaries of the city of Baltimore
(1998 population: 645 664). 12
<http://jama.ama-assn.org/issues/v287n6/rfull/#r12> Households were
selected using a stratified probability sampling design that selected
residences from the Baltimore Real Estate Property Registry. This registry
includes all propertiesboth taxable and tax-exemptwithin the city of
Baltimore. Two sample strata were disproportionately sampled to ensure
adequate representation of (1) young black men and (2) young adults living
in predominantly white US Census tracts with elevated levels of STDs (based
on Baltimore City Health Department [BCHD] STD surveillance statistics).
Operationally, these 2 strata comprised (1) households with an age-eligible
man drawn from census tracts with 95% to 100% black residents according to
the 1990 US Census; and (2) adults aged 18 to 35 years residing in 13 census
tracts that had the highest rates of reported gonococcal infection among
tracts with 0% to 9% black residents. A third crosscutting sample stratum
was created to accommodate the refielding of a 50% random subsample of cases
for which our quality control procedures could not verify the integrity of
the interview data (see below).
This sample design oversampled segments of the population that are known to
have higher rates of STDs (ie, young black men and whites living in US
Census tracts with high rates of reported STDs). Oversampling is routinely
used in household surveys to ensure adequate sample sizes for
difficult-to-survey or numerically rare segments of the population.
Probability sampling requires that every member of the population have a
nonzero probability of selection. Complex probability samples use
stratification and sampling at different rates in the design stage and
sample weighting (by the inverse of the sampling probabilities) at the
analysis stage to yield samples representative of the targeted population.
Our prevalence estimation uses sampling weights to adjust for the unequal
probabilities of selection across sample strata.
Informed Consent
A 2-stage procedure was used to obtain informed consent. Informed consent
(both oral and written) was first obtained from all survey participants
(aged 18-45 years) prior to the survey interview. A separate consent (both
oral and written) was obtained from respondents (aged 18-35 years)
participating in the urine testing. The informed consent process made
explicit that the urine would not be used for drug testing and that, in
compliance with state laws, specimens found positive for gonococcal and/or
chlamydial infection would be reported to the BCHD. The protocol for this
study was approved by institutional review boards at the Research Triangle
Institute and Johns Hopkins Medical Institutions.
Interview
Respondents completed a detailed survey on sexual behavior, prior STD
history, STD symptoms, drug and alcohol use, social attitudes and behaviors,
and individual background characteristics. Interview data were collected by
36 trained interviewers in the respondent's home. Interviewers were
instructed to conduct the interviews in a private place in the home or at an
alternate location where privacy could be ensured. They were specifically
instructed that they could not conduct an interview if another person was
listening. To satisfy another objective of the research program, respondents
were randomly assigned to complete the survey questionnaire using either
traditional survey procedures (ie, computer-assisted personal interview with
some paper-and-pencil self-administered questionnaires) or an audio
computer-assisted self-interviewing technology. 13-15
<http://jama.ama-assn.org/issues/v287n6/rfull/#r13> (Random assignment of
respondents to interview modes ensures that there will be no systematic
association between interview mode and the variable of central interest to
us NAAT-diagnosed gonococcal or chlamydial infection.) Data from these 2
interview modes are aggregated in this article. The survey took an average
of 26 minutes to complete. Respondents received $10 to $20 at the conclusion
of the interview.
Collection and Processing of Urine Specimen
At the conclusion of the interview, participants aged 18 to 35 years were
asked to provide a urine specimen for testing. Respondents who agreed to
provide a urine sample for screening received an additional $10 to $20.
N gonorrhoeae and C trachomatis were detected in urine specimens using a
ligase chain reaction (LCR) assay (Abbott Laboratories, North Chicago, Ill).
The LCR assay was performed according to the manufacturer's instructions.
Positive test results were reconfirmed by a repeat analysis using this same
procedure. If this second analysis was negative, the case was coded as
negative. (Repeat analyses were not available for 3 cases that tested
positive on initial testing. These cases were coded positive based on their
initial testing.)
Notification of Results
All respondents were given a telephone number they could call to learn of
their test results, and study staff used a succession of methods to attempt
to contact participants who tested positive (telephone, registered letter,
and, if refused or undelivered, regular mail). Free, expedited treatment at
one of the BCHD clinics was offered to all contacted subjects who tested
positive.
Quality Control
During the course of the study, a subset of interviewers' work was subject
to independent verification to confirm that the interview had been completed
and that a urine specimen had been requested if the respondent was 35 years
or younger. A verification interviewer (not part of the regular survey
staff) contacted the household to confirm the respondent's name,
participation in the survey, demographic information, date of interview,
whether a urine specimen had been collected, and whether the respondent had
been paid the monetary incentive. This procedure identified 7 interviewers
who appeared to have fabricated some of their interviews or to have
collected interview data and urine specimens from households other than
those selected into the sample. All of the interviews submitted by these
interviewers were subject to verification, and data were retained only if
the verification result was positive. (A full account of these procedures
has been presented elsewhere. 16
<http://jama.ama-assn.org/issues/v287n6/rfull/#r16> )
Over the course of the study, 56% of all completed survey interviews
included in the final database were subject to independent verification.
Statistical Analyses
Prevalence estimates were derived using case weights that are inversely
proportional to the probabilities of case selection and that incorporate a
poststratification weighting to ensure that the sample distribution matched
the 1997 US Census tabulation of the Baltimore population by race, sex, and
age. Statistical algorithms that take account of the impact of complex
sample designs on variance estimates, as implemented in the survey data
component of Stata 6.0, 17
<http://jama.ama-assn.org/issues/v287n6/rfull/#r17> , 18
<http://jama.ama-assn.org/issues/v287n6/rfull/#r18> were used in all
analyses and calculation of variance estimates. We tabulated frequencies of
demographic characteristics to obtain a descriptive profile of the sample.
Logistic regression and chi2 tests were used to assess the association
between estimates of infection status and other subject characteristics.
Tests of the equivalence of prevalence estimates for gonoccocal vs
chlamydial infections take account of the covariance that arises when
estimates are derived using measurements made on the same subjects.
Impact of Assay Performance on Estimated Prevalence
To assess the potential impact of assay performance on prevalence estimates,
sensitivity analyses were conducted using a plausible range of estimates for
the specificity (0.990-0.999) and sensitivity (0.90-0.94) of the LCR assays
used in this research. Past research indicates that NAAT assays have high
sensitivity (>0.90) and specificity (>0.99) for the detection of chlamydial
and gonococcal infections because genetic material from the target organisms
is detected. 19-24 <http://jama.ama-assn.org/issues/v287n6/rfull/#r19> In
the present study, specificity was optimized by retesting almost all
positive specimens and considering a specimen positive only if both initial
and repeat test results were positive. Sensitivity analyses were performed
using spreadsheets constructed in Excel 2000 (Microsoft, Redmond, Wash).
Impact of Missing Data on Estimated Prevalence
To assess the impact of respondents' refusal or inability to provide urine
specimens on our prevalence estimates, we used logistic regression to model
the likelihood that respondents would test positive for either gonococcal or
chlamydial infection based on a range of sociodemographic and behavioral
variables collected in the survey interview. This model was estimated using
data from those respondents who provided urine samples adequate for testing.
The parameter estimates derived for this model were then used to impute the
probability that individual nonrespondents in the urine collection would
have tested positive for either pathogen had they been tested. These imputed
probability values for respondents who did not provide a urine specimen were
combined with the actual gonococcal and chlamydial infection test results
for respondents who did provide specimens. The synthetic estimate derived by
this imputation process (8.1% for infection with C trachomatis and/or N
gonorrhoeae) was quite similar to the unadjusted estimate derived from
tested specimens alone (7.9%). Since imputation for nonresponse did not have
a substantial effect on the overall prevalence estimate, we used unadjusted
estimates based on complete data in our analyses.
Other Data Sources
In addition to prevalence estimates derived from LCR testing of urine
specimens, we derived alternate prevalence estimates from physician- and
laboratory-diagnosed cases of gonococcal and chlamydial infection reported
to the BCHD in 1998 (G. Olthoff, MHA, written communication, November 2,
2001). Health Department estimates are derived from the Baltimore STD
reporting system and eliminate instances (as duplicate reports) in which
infection with the same pathogen is reported in the same individual 2 (or
more) times within a 30-day period (W. Braithwaite, BA, written
communication, December 5, 2001). Reports of infection of the same
individual outside of this 30-day period are included in the case counts.
Alternate prevalence estimates were also derived from survey respondents'
answers to questions asking whether they had ever heard of gonorrhea and
chlamydia and, if so, had they been diagnosed as having these infections in
the 12 months prior to the survey. Respondents' answers provide 2 estimates
of the prevalence of diagnosed infection. The first and lower estimate
assumes that respondents who had not heard of a disease (gonorrhea or
chlamydia) had not been diagnosed as having the disease in the previous 12
months. A second and higher estimate assumes that persons who had never
heard of the infection were just as likely to have been diagnosed as having
this infection in the past 12 months as respondents who had heard of the
infection.
For both diagnoses reported to the BCHD and those reported by survey
respondents, we assume that diagnosis is accompanied by treatment, although
in a small but unknown number of cases this may not be true.
RESULTS
Survey Execution
Of the 3182 households selected for interview, 2727 (85.7%) were
successfully screened. Screening identified a total of 1224 English-speaking
adults who were between the ages of 18 and 45 years and eligible for
interview. Survey interviews were completed with 1014 respondents (82.8%)
between January 1997 and September 1998.
The protocol specified that only respondents between the ages of 18 and 35
years were eligible to provide urine for gonorrhea and chlamydia testing. Of
the 1014 respondents between the ages of 18 and 45 years who completed the
interview, 728 respondents aged 18 to 35 years were asked to provide urine
for testing. Of the 728 age-eligible respondents, 579 (79.5%) provided a
urine specimen adequate for testing, 119 (16.3%) refused to provide a urine
specimen, and 30 (4.1%) were not tested because of inadequate urine volume,
interviewer error, or other logistical problems. Table 1
<http://jama.ama-assn.org/issues/v287n6/fig_tab/joc10483_t1.html> presents
the unweighted numbers of adults providing urine samples and weighted
percentage distributions for selected sociodemographic groups.
Estimated Prevalence of Untreated Infections
Among Baltimore adults aged 18 to 35 years, we estimate the prevalence of
untreated chlamydial infection is 3.0% (SE, 0.8%) and the prevalence of
untreated gonococcal infection is 5.3% (SE, 1.4%) ( Table 2
<http://jama.ama-assn.org/issues/v287n6/fig_tab/joc10483_t2.html> ).
Overall, 0.4% (SE, 0.3%) of adults are estimated to have both infections
(data not shown), and 7.9% (SE, 1.6%) of Baltimore adults aged 18 to 35
years are estimated to have either gonococcal or chlamydial infection (or
both). The difference between the estimated prevalence of these 2 infections
is not statistically significant (P = .16). All respondents who reported a
diagnosis of gonococcal (unweighted sample of 9) or chlamydial (unweighted
sample of 13) infection in the past 12 months tested negative by LCR for the
diagnosed (and presumably treated) pathogen.
Table 2 <http://jama.ama-assn.org/issues/v287n6/fig_tab/joc10483_t2.html>
includes both weighted population prevalence estimates and unweighted counts
of the numbers of infections detected and subjects tested. The unweighted
sample counts represent the results of our NAAT analysis; they do not
provide valid estimates of the prevalence of infection in the population as
a whole or in any subpopulation. Since we used a complex sample design that
purposely oversampled certain segments of the population (see above), only
the weighted estimates can be used to make inferences about the prevalence
of NAAT-detectable infections in the population.
Impact of Assay Performance on Estimated Prevalence
Assuming the sensitivity of the LCR assay was 0.90 to 0.94 and specificity
was 0.990 to 0.999, sensitivity analysis indicates that the "true"
underlying prevalence of chlamydial infection would be 2.2% to 3.2%, given
our population prevalence estimate of 3.0%. For gonorrhea, the "true"
underlying prevalence would be 4.6% to 5.8%, given our population prevalence
estimate of 5.3%. This sensitivity analysis suggests that our prevalence
estimates are not substantially affected by the imperfection of the LCR
assay.
Untreated Infections by Sex, Race, and Age
The prevalence of gonococcal and chlamydial infections varies substantially
across subpopulations ( Table 2
<http://jama.ama-assn.org/issues/v287n6/fig_tab/joc10483_t2.html> ). We
estimate that 15.0% (SE, 3.7%) of black women have gonococcal and/or
chlamydial infections while the estimated infection rates are significantly
lower for black men (6.4% [SE, 2.1%]; P = .02) and nonblack women (1.3% [SE,
0.5%]; P<.001). Estimated prevalence was lower among nonblack men (2.8% [SE,
1.3%]) than among black men, although the difference was not significant.
For both blacks and for women, gonococcal infection appears to be more
prevalent than chlamydial infection, but this difference is also not
statistically significant.
Table 3 <http://jama.ama-assn.org/issues/v287n6/fig_tab/joc10483_t3.html>
shows a significant decline with age in the estimated prevalence of
NAAT-detectable chlamydial infections (P = .006 for trend) and subjects'
reports of diagnoses of gonococcal infections during the past 12 months (P =
.02 for trend). A parallel, although less uniform and nonsignificant, trend
occurs for chlamydial infections diagnosed in the past year.
Current untreated gonococcal infections show a different pattern. The
highest prevalence of detectable gonococcal infection (10.2% [SE, 3.3%])
occurs among persons aged 31 to 35 years. While the number of infections
detected is small (unweighted counts: 33/579 [aged 18-35 years] and 17/207
[aged 31-35 years]), the unexpectedly high prevalence estimated for
gonococcal infection among older respondents is unlikely to be due to the
small sample sizes. (The null hypothesis that the population prevalence of
gonococcal infections is equivalent among adults aged 31 to 35 years and
those aged 18 to 30 years is rejected with P<.001.) High estimated
prevalences of untreated gonococcal infections are observed among both men
(7.8%) and women (12.2%) in the group aged 31 to 35 years (data not shown).
Symptoms and Antibiotic Use
The high prevalence of untreated infections estimated for the Baltimore
population raises questions about the reasons why medical diagnosis and
treatment were not obtained. Interview data indicate that symptoms were
rarely reported among persons with untreated gonococcal or chlamydial
infections. Excluding persons receiving treatment for a gonococcal or
chlamydial infection in the previous 6 months, only 2.0% of currently
infected respondents reported dysuria (burning on urination) and 4.7%
reported discharge within the past 6 months. Untreated infections were found
less frequently among persons reporting dysuria during the preceding 6
months than among those who did not report this symptom (prevalence: 2.0% vs
8.8% [odds ratio {OR}, 0.21]; P = .08). Similarly, infections were less
likely to be reported among persons who report dripping or discharge in the
past 6 months than among those who did not, but this difference did not
approach statistical significance (4.7% vs 8.4% [OR, 0.54]; P = .43).
Persons who reported antibiotic use in the 6 months prior to testing were
less likely to test positive for gonococcal and/or chlamydial infection than
those who reported no antibiotic use in this period (4.4% vs 10.5% [OR,
0.40]; P = .04). In theory, variation in the use of antibiotics could
produce a negative association between symptom reporting and current
infection status if antibiotics were administered presumptively on the
reporting of dysuria or discharge. To control for this possibility, we
examined the relationship of symptoms and current infection status in
persons reporting no antibiotic use and no diagnosed gonococcal or
chlamydial infections in the 6 months prior to testing. A trend toward
asymptomatic infection remains (OR, 0.24 for dysuria; and OR, 0.32 for
discharge), however, with the diminished sample sizes, these results are not
statistically significant (P = .19 and P = .30, respectively).
Number of Treated vs Untreated Infections
Overall, 4566 gonococcal infections were diagnosed in persons aged 18 to 35
years and reported to the BCHD in 1998 ( Table 4
<http://jama.ama-assn.org/issues/v287n6/fig_tab/joc10483_t4.html> ). This
would represent a maximum population prevalence of 2.6% (under the
assumption that no person had 2 infections recorded during the year).
Interview data provided by our survey respondents suggest that between 4708
(2.7%) and 5231 (3.0%) individuals in this age group were diagnosed as
having (and presumably received treatment for) gonococcal infections in the
12 months prior to our survey. Based on NAAT assays of urine specimens, we
estimate that 9241 (5.3%) of this age group had a current and untreated
gonococcal infection at the time of our survey. The divergence in estimates
of diagnosed and undiagnosed gonococcal infections is most striking for
women. Three estimates of the number of women (aged 18-35 years) diagnosed
as having gonococcal infection annually in Baltimore lie in the range of
1272 (1.4%) to 2051 (2.3%). NAAT analysis of urine specimens from our
probability sample of this population leads us to estimate that 6087 women
(6.7%) were carrying an undiagnosed gonococcal infection at the time of the
survey.
For chlamydial infection, BCHD records indicate that 3664 infections were
diagnosed in this age group in 1998. This represents a maximum prevalence of
2.1%. Responses during the survey interview suggest that 5580 (3.2%) to 6975
(4.0%) of the population were diagnosed as having and presumably treated for
chlamydial infections in the 12 months prior to our survey. Testing of urine
specimens yields an estimate that 5231 (3.0%) of this age group had a
current and untreated chlamydial infection. Examination of the results by
sex indicates that only 391 men (0.5%) were diagnosed as having chlamydial
infections and reported to the BCHD in 1998 while our testing of urine
specimens yields an estimate that 1336 men in this age group (1.6%) had a
current untreated chlamydial infection. Male respondents reported diagnoses
of chlamydial infection by their health care providers at rates that are
considerably higher than recorded in BCHD statistics (1.9%-2.5% vs 0.5%).
This may reflect presumptive treatment (eg, for nongonococcal urethritis)
without diagnostic testing.
COMMENT
The foregoing estimates indicate that nearly 1 in 12 (7.9%) Baltimore adults
between the ages of 18 and 35 years has an untreated infection with either N
gonorrhoeae or C trachomatis. The estimated prevalence for black women is
greater than 1 in 7 (15.0%). Two important conclusions emerge when these
estimates, which represent undiagnosed infections prevalent in the
population, are compared with estimates of the number of infections
diagnosed annually. First, the combined number of gonococcal and chlamydial
infections that persist undiagnosed and untreated in this population exceeds
the number of infections that are diagnosed and treated in a given year.
Second, there appears to be a large reservoir of undiagnosed gonococcal
infections in Baltimore, particularly among women.
It is impossible to know the duration of the infections detected in this
study. We note, however, that nearly all of the detected infections occurred
among adults who reported no recent symptoms. In addition, elevated levels
of gonococcal infection were detected among older adults aged 31 to 35
years. The lack of symptoms and high levels of gonococcal infection among
the oldest sampled age group suggest that persistent infections may be
responsible for the high prevalence of untreated asymptomatic infections
detected in this study. Longstanding infections may represent low organism
burden, partial immunological clearance, 26
<http://jama.ama-assn.org/issues/v287n6/rfull/#r26> or infection with
organism strains that cause less symptomatic disease. 27
<http://jama.ama-assn.org/issues/v287n6/rfull/#r27> In some cases, these
persistent asymptomatic infections may be associated with significant
sequelae, such as infertility. In other cases, the clinical importance and
transmissibility of these infections is less clear. 28
<http://jama.ama-assn.org/issues/v287n6/rfull/#r28> Although there is some
uncertainty about the interpretation of NAAT-detected infections, we believe
our findings have 2 important implications.
First, prompt consideration should be given to strategies for improving the
diagnosis and treatment of asymptomatic infections in this population. The
urine-based NAAT assays used in this research are approved by the Food and
Drug Administration for diagnosis of gonococcal and chlamydial infections.
As such, we believe it is prudent to plan appropriate public health actions
in response to the high prevalence rates we have detected. Strategies for
reducing the prevalence of infection in this population might include
screening or routine testing in health care settings for the entire
population of young adults, including persons who formerly would be
considered to be at low risk of infection. (Such efforts will require
confronting issues that are beyond the scope of the present article,
including identification of appropriate methods for delivering and financing
such testing, and the role to be played by public health facilities and
private health care providers.)
In support of this recommendation, we note that Mehta et al 29
<http://jama.ama-assn.org/issues/v287n6/rfull/#r29> recently reported
testing 454 patients (aged 18-31 years) seeking medical care for reasons
other than STD symptoms at the adult emergency department at Johns Hopkins
Hospital and Health System (Baltimore, Md). Using urine-based NAAT assays,
investigators found that 9.3% of these patients tested positive for
chlamydial infection and 5.3% tested positive for gonococcal infection.
Their sample is not directly comparable with our own since they recruited
patients in a large Baltimore emergency department. However, both our
estimates and those of Mehta et al are derived from screening adult
populations outside of an STD care setting.
The second implication of our findings is that research is urgently needed
to improve our understanding of the clinical and public health significance
of NAAT-detectable infections. It is possible that NAAT assays are
identifying clinically inconsequential infections because of the assays'
ability to detect extremely low levels of viable organisms (ie, below the
infectious inoculum) or amplifiable DNA (or RNA) from residual pathogens
(ie, nonviable organisms) of past infections that are well on their way to
being cleared. One potentially informative line of research may be to
compare the transmissibility and clinical consequences of infections that
are detectable only by NAAT assay vs those that are detectable by
traditional assays. 30 <http://jama.ama-assn.org/issues/v287n6/rfull/#r30>
In addition to its substantive findings, the present study provides an
example of the feasibility and benefits of combining population survey
techniques and NAAT analysis of urine specimens in research on the
epidemiology of STDs. Such research can complement and enrich the
epidemiological insights gained from studies using case reporting systems
and studies of clinical and other special populations. Most importantly,
this research permits generalizations about the prevalence in the population
at largeor at least in that fraction of the population who consents to being
surveyed.
Interpretation of our research findings will benefit from replication. Since
teenagers both contract infections from and transmit infections to the adult
population, any replication should include this segment of the population.
Annual or biannual monitoring of STD prevalence using population survey
techniques in Baltimore and elsewhere could enrich our understanding of the
epidemiology of these STDs. It could also provide important guidance on the
appropriate roles of population prevalence data and STD case reports in
tracking trends in these STDs and identifying subpopulations that might
benefit from screening or other interventions designed to inhibit the spread
of these infections.
Author/Article Information
Author Affiliations: Program in Health and Behavior Measurement, Research
Triangle Institute, Washington, DC (Drs Turner, Rogers, H. Miller, and
Gribble); City University of New York, Queens College and Graduate Center,
Flushing, NY (Dr Turner); Statistics Research Division (Dr Chromy) and
Research Computing Division (Mr Cooley), Research Triangle Institute,
Research Triangle Park, NC; Division of Infectious Diseases, Department of
Medicine and Department of Epidemiology, University of North Carolina,
Chapel Hill (Drs W. Miller and Leone); Division of Infectious Diseases,
School of Medicine, Johns Hopkins University, Baltimore, Md (Drs Quinn and
Zenilman); National Institute of Allergy and Infectious Diseases, Bethesda,
Md (Dr Quinn).
Corresponding Author and Reprints: Charles F. Turner, PhD, Program in Health
and Behavior Measurement, Research Triangle Institute, 1615 M St NW,
Washington, DC 20036 (e-mail: [log in to unmask] <mailto:[log in to unmask]> ).
Author Contributions: Study concept and design: Turner, Rogers, H. Miller,
Gribble, Chromy, Cooley, Quinn, Zenilman.
Acquisition of data: Turner, Rogers, H. Miller, Gribble, Chromy, Cooley,
Zenilman.
Analysis and interpretation of data: Turner, Rogers, H. Miller, W. Miller,
Chromy, Leone, Quinn, Zenilman.
Drafting of the manuscript: Turner, Rogers, W. Miller, Leone.
Critical revision of the manuscript for important intellectual content:
Turner, Rogers, H. Miller, W. Miller, Gribble, Chromy, Cooley, Quinn,
Zenilman.
Statistical expertise: Rogers, W. Miller, Chromy.
Obtained funding: Turner, H. Miller.
Administrative, technical, or material support: Turner, Rogers, H. Miller,
Gribble, Leone, Cooley, Zenilman.
Study supervision: Turner, H. Miller.
Funding/Support: Primary support for this research was provided by NIH grant
R01-HD31067 to Dr Turner. Additional support was provided by the Research
Triangle Institute and by grant R01-MH56318 to Dr Turner, and grants
K24-AI01633 and U19-AI38533 to Dr Zenilman. Dr W. Miller received support
through the Clinical Associate Physician Program of the General Clinical
Research Center (RR00046), Division of Research Resources, National
Institutes of Health. Abbott Laboratories donated some of the LCR test kits
used in this study.
Acknowledgment: We thank Jeff Yuenger for his assistance in organizing the
laboratory testing and the survey operations staff of the Research Triangle
Institute for their fielding of the survey.
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