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Neisseria gonorrhoeae

by Real-time PCR with Reflex to Antibiotic resistance by Molecular Analysis

The sensitivity and specificity of the nucleic acid amplification


tests (NAATs) are clearly the highest of any of the test
platforms for the diagnosis of chlamydial and gonococcal
infections. Since accurate diagnosis is the goal, there is no
justification for the ongoing use of other technologies(1, 2).
- Centers for Disease Control and Prevention (CDC)



MDL provides detection of Neisseria gonorrhoeae by RealTime PCR, one of the most powerful and sensitive gene
analysis techniques available.
Sensitivity and specificity up to 99%.
Test results are typically available within 24-48 hours.
This test has been validated for detection of N. gonorrhoeae
using the OneSwab, UroSwab (males and females), and
ThinPrep.

Epidemiology

Gonorrhea is the second most commonly reported bacterial


STD in the United States with an estimated 700,000 new N.
gonorrhoeae infections occuring each year (7).
Due to the fact that gonococcal infections among women are
frequently asymptomatic, targeted screening of young women
at increased risk for infection is a primary component of
gonorrhea control in the United States (7).

Laboratory Diagnosis

Pathogenesis

Neisseria gonorrhoeae, a Gram-negative diplococci, is the


causative agent of gonorrhea.
Due to its affinity for columnar or pseudo stratified epithelium, it
is most commonly detected in the genital tract with the primary
site of involvement being the endocervical canal and transition
zone of the cervix.
N. gonorrhoeaes unique ability to alter surface structures
allows increased pathogenicity, facilitates epithelial surface
attachment, and enables evasion of the hosts immune
response.
Transmission of N. gonorrhoeae occurs almost exclusively
through sexual contact, though it can also be transmitted via
the passage of a neonate through an infected mothers birth
canal or via autoinoculation from the hands of an infected
person to their eye.
Incubation time for this infection is typically 3-5 days and
transmission more frequently occurs from male to female.
Some risks factors for infection include: low socioeconomic
status, early onset of sexual activity, unmarried status, a
history of previous gonorrhea infection, illicit drug abuse, and
prostitution.

chorioamnionitis, premature birth, intrauterine growth retardation,


neonatal sepsis, and postpartum endometritis.
During vaginal delivery with an infected mother, 30% to 35%
of neonates will acquire Neisseria gonorrhoeae which, if left
untreated, can progress to corneal ulceration and scarring, as
well as blindness called gonorrheal ophthalmia neonatorum.

Diagnosis of infections with N. gonorrhoeae has traditionally


relied upon Gram stain, culture, and immunochemical
techniques. Although culture techniques may be highly
specific, sensitivity is greatly impacted by the adequacy of the
clinical specimen and transport conditions, particularly when
transporting to off-site facilities.
Due to the genome plasticity of N. gonorrhoeae strains
circulating in the population, this bacterium has developed
resistance to multiple classes of antimicrobial agents, resulting
in decreased efficacy for gonorrhea therapy. An increase of
ceftriaxone-resistant N. gonorrhoeae demonstrated a similar
pattern to previous reports in Japan and Southeast Asia that
prompted the CDC to remove ciprofloxacin from the treatment
guidelines as a primary antibiotic (1-3).
In August 2012, the CDC called for Ceph-R NG surveillance
through N. gonorrhoeae antibiotic susceptibility testing for
patients that have failed treatment (3). Although susceptibility
testing by culture remains the standard for antibiotic
susceptibility determination in clinical microbiology, there are
inherent growth-related issues that can delay results by as
much as three days or more.
Known mechanisms of antibiotic resistance in N. gonorrhoeae
are linked to mutations in the chromosomal DNA as well as
the presence of plasmid-borne genes. Surveillance of genetic
markers of antibiotic resistance is important for the prediction of
clinical resistance as the antibiotic susceptibility signatures of
individual N. gonorrhoeae strains differ.

Clinical Significance

Clinical manifestation in men usually includes symptomatic


urethritis; however, pharyngeal, anorectal, and disseminated
infections are also possible.
In women, infections are often asymptomatic; however, when
manifested, symptoms may include: vaginal discharge, dysuria,
intermenstrual bleeding, menorrhagia, pelvic discomfort,
infection of the periurethral glands, Bartholin glands, and
anorectum.
Due to the fact that gonorrhea can have serious consequences
for both mother and neonate, it is crucial to screen pregnant
women for infection who reportedly have an incidence of
gonorrhea during pregnancy as high as 10%.
Complications that can occur during pregnancy include: amniotic
infection syndrome, premature rupture of the membranes,

NOTE: PenR = penicillinase producing Neisseria gonorrhoeae and chromosomally mediated


penicillin-resistant N. gonorrhoeae; TetR = chromosomally and plasmid mediated tetracyclineresistant N. gonorrhoeae; and QRNG = quinolone-resistant N. gonorrhoeae.

Figure 1: Gonococcal isolate surveillance project (GISP)-penicillin,


tetracycline, and ciprofloxacin resistance among GISP isolates, 2010 (7).

Test 167 Neisseria gonorrhoeae by Real-Time PCR (Reflex


to Antibiotic Resistance by Molecular Analysis) developed
by MDL, offers a valuable diagnostic tool for the reliable
detection of genetic determinants of antibiotic resistance,
thereby predicting antibiotic susceptibility of individual N.
gonorrhoeae strains in a given clinical specimen. This test
addresses the problem of genetic variability in N. gonorrhoeae
and delivers a prognostic recommendation for antibiotic therapy
in a personalized manner.

Medical Diagnostic Laboratories, L.L.C. www.mdlab.com 877.269.0090

Table 1: Comparison of Multiple Assay Systems for the Detection of Neisseria gonorrhoeae.
Test

Prevalence (%)

Sensitivity (%)

Specificity (%)

PPV (%)

NPV (%)

References

PCR

100

7.8

100

99.4

93.4

100

(17)

Amplicor

2238

5.2

96.3

98.7

80.2

99.8

(18)

Aptima Combo 2

1479

8.6

99.2

98.7

88.1

99.9

(19)

BD Probe Tec

1411

8.1

97.2

99.4

91.6

99.6

(20)

GEN-PROBE
(Pace 2)

1750

8.7

97.1

99.1

90.6

99.8

(21)

Culture

866

4.5

50.0

97.1

40.0

98.0

(22)

= Unless otherwise noted, all specimens are swabs


= Calculated data

Screening

Table 2: Summary of screening for N. gonorrhoeae infection by nucleic

acid amplification testing (NAAT) (derived from 7).


Women

Annual routine screening for all sexually active women at risk


for infection.
Screening at the first prenatal visit for all pregnant women at risk
or living in a high prevalence area.
In women with cervicitis via either vaginal, cervical, or urine
samples.

Men who have sex with men (MSM)

Screening for urethral infection via nucleic acid amplification


testing (NAAT) of urine in all men who have had insertive
intercourse the preceding year regardless of condom use.
Screening for rectal infection via nucleic acid amplification testing
(NAAT) of a rectal swab in all men who have had receptive anal
intercourse during the preceding year.
Screening for pharyngeal infection via nucleic acid amplification
testing (NAAT) in all men who have had receptive oral intercourse
during the preceding year.

Both Men and Women

Newly diagnosed HIV infection

Treatment
Table 3: Current Recommendations from the CDC for adults, adolescents

& children >45 kg: urogenital, rectal infection with N. gonorrhoeae (16).
Recommended Regimens
Ceftriaxone 250 mg IM in a single dose PLUS
Azithromycin 1 g orally in a single dose
OR
Doxycycline 100 mg orally twice a day for 7 days
Alternative Regimens: If ceftriaxone is not an option
Cefixime 400 mg orally in a single dose PLUS
Azithromycin 1 g orally in a single dose
OR
Doxycycline 100 mg orally twice a day for 7 days

Due to the concerns for developing patterns of antimicrobial


resistance, most current recommendations for treatment
should be followed. Guidance can be obtained from the CDC
website (http://w ww.cdc.gov/std/gisp) and state and local
health departments.
If treatment is still unsuccessful, contact the CDC for a
consultation.
Complete treatment guidelines for Chlamydia are available
from the CDC http://www.cdc.gov/std/treatment/2010/vaginaldischarge.htm. (Accessed March 28, 2012).

REFERENCES:
1. Miller WC, Ford CA, Morris M, et al. 2004. Prevalence of Chlamydia
Infections Among Young Adults in the United States. JAMA 291:22292236.
2. Monif GR, Baker DA. Infectious Diseases in Obstetrics and
Gynecology, Fifth Edition. New York, NY: The Parthenon Publishing
Group; 2004:222-233.
3. Mandell, GL, Bennett JE, Dolin R. Mandell, Douglas, and Bennetts
Principles and Practices of Infectious Diseases, Vol 2. Philadelphia:
Churchhill Livingstone; 2000:2242-2256.
4. Faro S, Soper DE. Infectious Diseases in Women. Philadelphia: W.B.
Saunders Company; 2001:435-450.
5. Girdner JL, Cullen AP, Salama TG, et al. (1998). ASM Meeting.
6. Donders GF, VanGerven V, de Wet HG, et al. 1996. Scan J Infect Dis.
28:559-562.
7. CDC. 2010. Sexually Transmitted Disease Guidelines. MMWR Vol. 59,
no. RR-12.
8. Girdner JL, Cullen AP, Salama TG, et al. 1998. ASM Meeting.
9. Vlaspolder F, Mustaers JA, Blog F, et al. 1993. J Clin Microbiol
31:107-110.
10. Cullen A, He L, Arthur P, et al. 1998. ASM Meeting.
11. Donders GF, VanGerven V, de Wet HG, et al. 1996. Scan J Infect Dis
28:559-562.
12. Johnson RE, Newhall WJ, Papp JR, et al. 2002. Screening
tests to detect Chlamydia trachomatis and Neisseria gonorrhoeae
infections--2002.
13. CDC. 2002. MMWR Recomm Rep 2002 18;51(RR-15):1-38.
14. van Doornum GJ, Schouls LM, Pijl A, et al. 2001. Comparison
between the LCx Probe System and the COBAS AMPLICOR System
for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae
Infections in Patients Attending a Clinic for Treatment of Sexually
Transmitted Diseases in Amsterdam, The Netherlands. J Clin Microbiol
39(3):829-835.
15. Palmer HM, Mallinson H, Wood RL, Herring AJ. 2003. Evaluation of
the Specificities of Five DNA Amplification Methods for the Detection of
Neisseria gonorrheae. J Clin Microbiol 41(2):835-837.
16. CDC. 2010. Update to CDCs Sexually Transmitted Diseases Treatment
Guidelines, Oral Cephalosporins No Longer a Recommended
Treatment for Gonococcal Infection. MMWR 61(31):590-594.
17. Gaydos CA, et al. 2003. Performance of the APTIMA Combo 2 assay
for detection of Chlamydia trachomatis and Neisseria gonorrhoeae
in female urine and endocervical swab specimens. J Clin Microbiol
41(1):304-9.
18. Van Der Pol B, et al. 2001. Multicenter evaluation of the BDProbeTec
ET System for detection of Chlamydia trachomatis and Neisseria
gonorrhoeae in urine specimens, female endocervical swabs, and male
urethral swabs. J Clin Microbiol 39(3):1008-16.
19. Crotchfelt KA, et al. 1997. Detection of Neisseria gonorrhoeae and
Chlamydia trachomatis in genitourinary specimens from men and
women by a coamplification PCR assay. J Clin Microbiol 35(6):1536-40.
20. 510(k) Summary, http://www.fda.gov/cdrh/pdf/k974503. pdf. Device
name: Roche Amplicor CT/NG Test For Neisseria gonorrhoeae.
Accessed 06/2007.
21. Vlaspolder F, et al. 1993. Value of a DNA probe assay (Gen-Probe)
compared wh that of culture for diagnosis of gonococcal infection. J Clin
Microbiol 31(1):107-10.
22. Danders GG, et al. 1996. Rapid antigen tests for Neisseria gonorrhoeae
and Chlamydia trachomatis are not accurate for screening women with
disturbed vaginal lactobacillary flora. Scand J Infect Dis 28(6):559-62.

Medical Diagnostic Laboratories, L.L.C. www.mdlab.com 877.269.0090