Transcript the presentation - IUSTI Marrakesh 2016 :: Home

The Changing Paradigms of Who, Where,
and How to Screen for Chlamydia
Charlotte A. Gaydos, MS, MPH, DrPH
Professor, Division of Infectious Diseases
Johns Hopkins University
Baltimore, Maryland
Marrakesh IUSTI
May 9-12, 2016
Chlamydia Symposium
Chlamydia: The Good, the Bad, and
The Promising
Disclosures
• I have received funding for research
grants and/or have been a lecturer for
Becton Dickinson, Gen-Probe Hologic,
Abbott Molecular, Siemens Health Care
Diagnostics, Cepheid, and Quidel
Background
• Chlamydia trachomatis is a highly
prevalent STI worldwide and
screening is needed in order to
control the epidemic of
undiagnosed and untreated
infections
• A paradigm shift is needed as
new recommendations, places to
test, and new diagnostic tests
become available
Estimated Prevalence of
Sexually Transmitted Infections
in the World
(Total 2,993,200,000)
Objectives
• Discuss new recommendations for whom to screen based on
age and sexual preference
WHO
• Review use of NAATs and non-genital specimens, such as
rectal and oral-pharyngeal samples
HOW
• Examine use of non-invasive specimen types available and
screening outside a clinic
WHERE
• Assess how of point-of-care (POC) tests for chlamydia allow
opportunities to enable patients to be immediately treated
according to an exact diagnosis
HOW
Who Shall We Screen?
European Guidelines: Indications for laboratory testing
(Level of evidence IV; Grade C recommendation)
. Risk factor(s) for C. trachomatis infection and/or other STI (age<25 years,
new sexual contact in the last year, more than one partner in the last year
. Symptoms or signs of urethritis in men
. Cervical or vaginal discharge with risk factor for STI
. Acute epididymo-orchitis in males aged <40 years or w/ risk factors for STI
. Acute pelvic pain and/or symptoms or signs of PID
. Proctitis/proctocolitis according to risk
Who Shall We Screen?
Purulent conjunctivitis in a neonate or adult
. Atypical neonatal pneumonia
. Persons diagnosed with other STI
. Sexual contact of persons with an STI or PID
. Termination of pregnancy
. Any intrauterine interventions or manipulations
Who Shall We Screen?
September Chlamydia Gonorrhea The USPSTF recommends
2014*
screening: women
screening for chlamydia in
sexually active women age
24 years or younger and in
older women who are at
increased risk for infection.
B
September Sexually transmitted
2014*
infections counseling
B
The USPSTF recommends
intensive behavioral
counseling for all sexually
active adolescents and for
adults who are at increased
risk for sexually transmitted
infections.
LeFevre ML. Screening for Chlamydia and Gonorrhea: Annals of internal medicine. Sep 23 2014.
Who Shall We Screen?
Women:
•Sexually active women < 25 years of age
•Sexually active women aged 25 years & older at increased risk
•Retest approximately 3 months after treatment
Pregnant Women:
•All pregnant women under 25 years of age
•Pregnant women, aged 25 and older if at increased risk
•Retest in 3rd trimester for women < 25 years of age or at risk
•Pregnant women with chlamydial infection should have a testof-cure 3-4 weeks after treatment and be retested within 3
months
Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines, 2015.
Who Shall We Screen?
Men:
•Consider screening young men in high prevalence clinical settings or
in populations with high burden of infection (e.g. MSM)
Men Who have Sex With Men (MSM):
•At least annually for sexually active MSM at sites of contact (urethra,
rectum) regardless of condom use
•Every 3 to 6 months if at increased risk
Persons with HIV:
•For sexually active individuals, screen at first HIV evaluation, and at
least annually thereafter
•More frequent screening for might be appropriate depending on
individual risk behaviors and the local epidemiology
Objectives
• Discuss new recommendations for whom to screen based on
age and sexual preference
WHO
• Review use of NAATs and non-genital specimens, such as
rectal and oral-pharyngeal samples
HOW
• Examine use of non-invasive specimen types available and
screening outside a clinic
WHERE
• Assess how of point-of-care (POC) tests for chlamydia allow
opportunities to enable patients to be immediately treated
according to an exact diagnosis
HOW
CDC Recommendations for the LaboratoryBased Detection of Chlamydia trachomatis
and Neisseria gonorrhoeae — 2014
• NAATS are recommended
for genital infections
 Vaginal swabs for women
 Urine for men
 Endocervical/female
urine OK
 Self-collected approved
• NAATs recommended for
rectal and oropharyngeal
infections (not FDA cleared)
Papp JR, Schachter J, Gaydos CA, Van Der Pol B. Recommendations for the laboratory-based
detection of Chlamydia trachomatis and Neisseria gonorrhoeae- 2014. MMWR 2014;63(RR-02):1-19.
How Shall We Screen?
All 5 commercial companies who sell NAATs have
approval for self- collection of vaginal swabs and
urines as well as clinician-collection of cervical
swabs.
How does the clinician decide which sample type to
submit for testing?
Let’s look at some data
Clinician Collected vs. SelfCollected Vaginal Swabs: Aptima
Clinician Collected vs. SelfCollected Vaginal Swabs: Aptima
Vaginal swab specimens allowed sensitive and specific
detection of CT and GC in the APTIMA assays
Vaginal swabs identified as many infected patients as
endocervical swabs and more than FCUs
Patient-Collected Vaginal Swab ACT (pkg. insert)
Asymptomatic: Sens 98.4%;
Spec 95.6%
Clinician Collected Vaginal Swab ACT (pkg. insert)
Symptomatic: Sens 96.5%
Spec 95.3%
Asymptomatic: Sens 98.4%
Spec 94.5%
Schachter JCM 2005
Clinician Collected vs. SelfCollected Vaginal Swabs CT: m2000
Clinician collected Sym
Asym
92.5%
87.2%
Self-collected
94.7%
84.8%
Sym
Asym
No statistical difference
Performance of the Abbott RealTime CT/NG for Detection of Chlamydia
trachomatis and Neisseria gonorrhoeae
Gaydos et al. JCM, 48:3236–3243, 2010
Vaginal Swabs CT Comparison: ProbeTec
Clinical Evaluation of the BD ProbeTec™ Chlamydia trachomatis Qx Amplified
DNA Assay on the BD Viper™ System With XTR™ Technology
Taylor et al. JCM 38:603-609, 2011
Cobas 4800
Van Der Pol STD 40:247-250, 2013
Cobas 4800
CT 248
detected
Vag 232 +
Vag 16 -
Distribution of positive results by sample type. Chlamydia results
Van Der Pol STD 40: 247-250 2013
Results CT/NG 1,722 female & 1,387 males
Xpert CT/NG vs. Patient Infected Status
Specimen
Sensitivity
Specificity
CT Cervical
CT Vaginal
CT Female Urine
97.4%
98.7%
97.6%
99.6%
99.4%
99.8%
NG Cervical
NG Vaginal
100%
100%
100%
99.9%
NG Female Urine
95.6%
99.9%
CT Male Urine
NG Male Urine
97.5%
98.9%
99.9%
99.9%
Gaydos et al. J Clin Microbiol. 51:1666-1672, 2013
STD Clinic Collection Aptima
•Percent Positivity according to infected patient
status for chlamydia 11.1% (36/324)
•N= 319 cervical swabs; 322 self-administered vaginal swabs (SAS);
324 urines
Specificity (%)
Sensitivity (%)
100
94.3
94.4
91.4
90
80
70
60
50
Cervical
Vaginal
Gaydos et al STD 2009
Urine
99.6
100
98
96
94
92
90
88
86
84
82
80
Cervical
100
Vaginal
100
Urine
Rectal and Oropharyngeal Swabs
• NAATs recommended for rectal and oropharyngeal
infections (not FDA cleared)
• Labs must perform own verification/verification studies
Proportion of Infections Detected by Rectal
or Genital Sampling
1
100%
11
90%
55
80%
70%
10
80
60%
14
50%
29
Rectal Only
Both
Genital only
40%
30%
9
20%
10%
13
55
17
24
0%
CT Male
GC Male
Van Der Pol, BASHH 2012
CT Female
GC Female
Objectives
• Discuss new recommendations for whom to screen based on
age and sexual preference
WHO
• Review use of NAATs and non-genital specimens, such as
rectal and oral-pharyngeal samples
HOW
• Examine use of non-invasive specimen types available and
screening outside a clinic
WHERE
• Assess how of point-of-care (POC) tests for chlamydia allow
opportunities to enable patients to be immediately treated
according to an exact diagnosis
HOW
Where Shall We Screen?
Standard:
New venues to recruit and screen:
STD/STI Clinics
GUM Clinics
Hospital Clinics
Emergency Departments
Primary Care Doctors
Adolescent Clinics
High School Clinics
College Clinics
Internet
Home
Health Fairs
Vans and Privacy Shelters
Pharmacies
Internet: www.iwantthekit.org June 2004- April 2016
FEMALE Vaginal (N =6900) (2004) MALE Penile (N = 3700) (2006)
CT: prevalence
GC prevalence
TV prevalence
7.05%
0.86%
6.5%
CT: prevalence
GC prevalence
TV prevalence
7.82%
0.74%
2.38%
FEMALE Rectal (N = 1198) (2009)
MALE Rectal (N = 769) (2009)
CT: prevalence
GC prevalence
TV prevalence
CT: prevalence
GC prevalence
TV prevalence
7.10%
0.92%
5.85%
7.28%
4.16%
0.65%
Am J Public Health.
2014;104:2313–
2320.
Results. During a 3-month period, 217 women aged 18 to 30 years enrolled;
67% returned the kit. Of these, 92% viewed their results online. STI prevalence
was 5.6% (chlamydia and trichomoniasis). All participants with STIs received
treatment either the same day at a pharmacy (62%) or within 7 days at a clinic
(38%). Among participants completing follow-up surveys, 99% would recommend
the online eSTI system to a friend, and 95% preferred it over clinic-based
testing within a study.
STD 42:13-19, 2015
STD 38:815-820 2011
Where: Vans, Health Fairs, & Privacy Shelters
Providing mobile point-of-care and near-patient STI testing to the general
population is feasible and acceptable. 42 tested
Hess EA, et al. Feasibility and acceptability of point-of-care testing for sexually transmissible
infections among men and women in mobile van settings. Sexual Health. 12:71-72, 2015.
Cincinnati Children's Hospital Medical Center
Among 27 men and 58 women 8 other
gender, a majority reported self-sampling
in a privacy shelter as “very acceptable”
Pittman et al. Patient acceptability and feasibility of self-collecting genital samples
for Chlamydia and gonorrhea testing in community settings using privacy shelters
SAHM 2016
Where Shall We Screen? Pharmacies?
Retail Clinics, Academic Thought Leaders & Diagnostic Technology Teams to Share
Opportunities for POC Testing
According to a recent report by Accenture, nearly 3,000 retail health clinics are expected
by 2017.
Meanwhile, 95% of the nation's 60,000 pharmacies are providing immunizations
Consumers see their local pharmacy, a place traditionally reserved for medications and
greeting cards, as a stop for acute care and chronic disease management.
Currently, about 18% of pharmacies hold a CLIA waiver allowing them to perform
diagnostic and screening tests. Given the convenient locations and hours as well as the
trust consumers already have in their pharmacists, there remains huge opportunity for
growth.
Objectives
• Discuss new recommendations for whom to screen based on
age and sexual preference
WHO
• Review use of NAATs and non-genital specimens, such as
rectal and oral-pharyngeal samples
HOW
• Examine use of non-invasive specimen types available and
screening outside a clinic
WHERE
• Assess how of point-of-care (POC) tests for chlamydia allow
opportunities to enable patients to be immediately treated
according to an exact diagnosis
HOW
ASSURED Criteria for POC
Affordable
by those at risk of infection
Sensitive
few false negatives
Specific
few false positives
User-friendly
simple to perform: 3-4 steps, minimal training
Rapid and Robust
rapid:
robust:
enable treatment at first visit
no refrigerated storage
Equipment-free
easily collected non-invasive specimens
Delivered
delivered to end-users
http://www.who.int/std_diagnostics/about_SDI/priorities.htm
POC Tests for STIs
• POC tests are desired by clinicians and patients
• Many are not yet accurate enough or able to be performed
in a short period of time
• Promising NAAT POC tests are in the pipeline
GeneXpert
(FDA: near patient now; faster coming)
Atlas Genetics (promising reports; CE marked)
Many Others Coming
Needs Assessment of Clinicians:
Build Your Own Test
• For which organisms do Clinicians want a POC
test? (Most say chlamydia)
• How sensitive?; (most important -90-99%)
• How specific? (99%)
• How fast does it have to be? (-20 min)
• What about cost? (second most important- $20)
• What about equipment? (no or little equipment)
Forced Choice Questions used in a survey with multivariate analysis
Hsieh Y-H et al. Plos One vol 6, issue 4, e19263, 2011.
Hsieh Y-H et al. Point of Care 11:126-129, 2012
What about Patients Needs?
• Willingness to wait is important
• Willingness to self-collect
specimens is important
• Willingness to pay is important
Patient Focus Group and Clinic
Questionnaire about POC Tests (N =371)
Specimen Type
Preference
Percent
Willingness Percent
to Wait
Cervical
Vaginal
Urine
15.4%
50.9%
33.7%
20 min
59.0%
40 min
20.8%
60 min
10.8%
90 min
9.4%
Willingness to Pay Percent
$10
46.6%
$20
31.0%
$30
10.8%
$40
2.7%
$50
8.9%
Self –collected vaginal swabs
3.0%
16.1%
80.9%
easy
hard
OK
Barnes et al. 2014 CDC STD Conf, Atlanta GA
POC tests for STIs: What do “end users” want?
(N=58, 5 focus groups)
)
• Favorable POCTs (Rapid, Easy to read, Simple to use)
•
•
•
•
Home testing acceptable – better privacy
Clinic-based- definitive results & immediate treatment
Barriers- cost and ability to read and perform tests
Hispanic patients questioned home test reliability,
wanted bi-lingual
instructions
Rompalo et al. Sexual Health 2013;10:541-545
• An ‘ASSURED’ POC test for chlamydia
is 89:88-89
yet to become
STI: 2013;
available
•
Netherlands compared three CE-marked POC tests (one
Currently
tests are
limited
by their
enzymaticavailable
and otherPOC
two antigen
tests)
for diagnostic
performance
cost.
performance and
in a high
CT-prevalence population (11%),
compared with NAATs over 8-months
• Further
studiesofare
assess theand
‘rapid
test
The sensitivity
therequired
tests was to
disappointing,
ranged
paradox’;
and
acceptability.
from 12%patient
to 27% in
772staff
women
tested
van Dommelen et al. Alarmingly poor performance in Chlamydia trachomatis
point-of-care testing. Sex Transm Infect 2010;86:355–9.
A New Near-Patient Model of Care
Dean Street Express, London England
Asymptomatic STI screening
Walk in: 30 min on site
Nurse-led service
Better resource management
Results within hours
Immediate treatment
The Patient Experience
Asympto.
screening
Walk In
No
stigma
Private self-check in
No
logistics
Sample transport
Reducing
human error
Sample
confidence
Programmed test request
Quality of
service
Fast sample processing
Self-directed
care
Automated results via text
Self collected sample
Patient
satisfaction
Online booking for follow up
Potential to Impact Outcome
• Faster Results: From 183 hours to 4 hours
• Quicker Treatment: 80% reduction in time to treatment
• Reduced Waiting Time: From 2 hours to 32 minutes
• Less Patients Lost to Follow-Up: From 15.6% to 3%
• High Uptake: Monthly increase in testing ~600%
• Rated “Excellent” by 94% of users
Barriers to implementation of POCTs
•
•
•
•
•
•
•
•
•
•
Financial viability
Money for instruments and consumables
Obtaining CLIA certificate
Verifying/validating the new test
Policies and procedures (training manuals)
Operator training (recertification, proficiency)
Getting results into the EMR (interface- $7K?)
Space
Work Flow Disruption
Billing and Reimbursement
Conclusions: Who, Where, and How
New guidelines for screening and treating individuals are
available from professional organizations; NAATs are
recommended
Non-invasive sample types are approved by all 5 commerciallyavailable NAATs; Approval for collection outside of clinic is
needed
Possible: health fair, pharmacy, recruitment via the Internet, and
on mobile vans and in privacy shelters
POC tests allow rapid diagnosis/treatment
POC tests could potentially allow self-testing to reduce the
incidence of chlamydial infections globally