- Email: [email protected]
The Resurgence of Chlamydia trachomatis
THE RESURGENCE OF CHLAMYDIA TRACHOMATIS Marc Steben, MD, CCFp, FCFP Direction risques biologiques, environnementaux et occupationnels, Institut national de sante publique du Quebec, and Vulvo-vaginal Disease Clinic, Oncology Gynecology Department, Hopital Notre-Dame, Centre hospitalier de l'Universite de Montreal, Montreal QC
Abstract: The objective of the review is to alert reproductive-care providers to the unexpected resurgence of Chlamydia infections and to new findings related to complications associated with Chlamydia infection. Data sources consisted of national and local guidelines and literature searches of MEDLINE with the heading Chlamydia infections 2002 and 2003. The complications of Chlamydia infections are considered to be longterm, and may include debilitating pain, infertility, tubal pregnancy, cancer, and HIV infection. Only a strong diseasemanagement response from reproductive-care providers, using new diagnostic techniques and simpler treatment regimens, as well as a strong public health reaction, will be effective to limit the scourges of Chlamydia infection in the female population. Resume: La presente analyse a pour objectif d'eveiller I'attention des fournisseurs de soins genesiques sur la recrudescence inatten due des infections a Chlamydia, ainsi que sur les nouveaux resultats de recherche lies aux complications associees aces infections. Des lignes directrices nationales et locales et des recherches documentaires dans MEDLINE (en utilisant les mots cles Chlamydia infections 2002 and 2003) ont ete utilisees a titre de sources de donnees. Les complications des infections a Chlamydia sont considerees comme etant a long terme et peuvent inclure la douleur debilitante, I'infertilite, la grossesse tubaire, Ie cancer et I'infection au VIH. Seule une solide gestion therapeutique de la part des fournisseurs de soins genesiques (faisant appel a de nouvelles techniques diagnostiques et a des schemas therapeutiques simplifies), conjuguee a une forte reaction de la part du secteur de la sante publique, parviendra a endiguer Ie fleau de I'infection a Chlamydia au sein de la population feminine.
J Obstet
INTRODUCTION
Genital Chlamydia trachomatis (CT) is a sexually transmitted infection (511) caused by the bacterium Chlamydia trachomatis. Females are disproportionately affected by the complications of this infection. 1,2 Optimism about the decreasing rates of CT flourished3 following the introduction of nucleic acid amplification techniques (NMTs) for diagnosis and screening purposes, and the availability of a simple unique oral dose of azithromycin for the treatment of uncomplicated urogenital infection. 4 This optimism has subsequently abated as new risk factors, as well as the re-emergence of old risk factors, have helped CT rebound to heights not seen for more than a decade. 5 Confronted with this worrisome resurgence, Montreal Public Health authorities released a plan of action 5 requiring "an energetic and coordinated response" from all reproductive-care providers to: • promote the adoption of safer sexual practices, • recognize the signs and symptoms of CT infections and perform appropriate diagnostic tests, • recognize, in the absence of signs and symptoms, the presence of risk factors, and perform appropriate screening tests, • treat infected people according to national standards, and • evaluate and treat all the sexual partners of infected persons within the 60-day recommended window period without delay.s New data are emerging about the deleterious effect that CT has on functions of infected cells, making this review necessary.6
Gynaecol Can 2004;26(6):552-9. METHODS
KeyWords Chlamydia trachomatis; Chlamydia infections; sexually transmitted diseases, bacterial - prevention and control; communicable disease control; contact tracing Competing interests: None declared. Received on October 14, 2003 Revised and accepted on April 9, 2004
Data sources consisted of national and local guidelines, and literature searches of MEDLINE using the key words" Chlamydia trachomatis," "Chlamydia infection," "sexually transmitted infection - bacterial," "prevention and control," "communicable disease control," and "contact tracing." EPIDEMIOLOGY
According to Health Canada, the estimated worldwide annual JOGC _JUNE 2004
termination of pregnancy in Lasalle, Quebec, and in Calgary, Alberta, was 8.5%, with bacterial vaginosis, casual sex, history of CT, and history of STI being significant risk factors. 5 New risk factors have recently emerged, such as sexual encounters organized through chat-rooms,15 casual sex during travel abroad,16 and rave parties. 17 These factors have all been associated with high-risk sexual activities in all patient groups, but except for their association with the acquisition of syphilis in gay men, these new risk factors have not yet been associated with higher rates ofSTIs in heterosexual persons. 6
incidence of CT cases in 1995 was 89 million, the greatest number being in Asia, followed by sub-Saharan Mrica. 7 In the United States, the reported rates ofCT infection have risen from 51 per 100 000 persons in 1987 to 278 per 100 000 persons in 2001. 8- 10 In Canada, CT is the most frequently reported bacterial infection (Table 1).3 Rates for women are at least 2 to 7 times higher in the age populations most at risk for CT complications when compared to risks for men of the same age group. 13 In Montreal, the number of reported cases of Chlamydia infection decreased by 65% from 1990 to 1996, but increased by 75% from 1996 to 2001 (Figure 1). Women continue to be the most affected (70% of all cases), especially those aged 15 to 24 years. The incidence rate in Montreal, in 2003, was 1433.2 cases per 100 000 among 15- to 19-year-old women, and 1871.2 cases per 100 000 among those aged 20 to 24 years. 14 These rates are 2 to 3 times higher than the target of 500 per 100 000 set for Canadian women in these age groups for the year 2000. 5 The incidence of Neisseria gonorrhoeae, Treponema pallidum, and CT infection, the 3 most common STIs, is increasing in most large cities. However, Neisseria gonorrhoeae and Treponema pallidum infections are diagnosed mostly in homosexual men, while CT is seen mostly in heterosexual men and women.
CUNICAL PRESENTATIONS TRANSMISSION
Genital CT is transmirted through direct genital-to-genital contact with an infected individual, who is most frequently asymptomatic. 8 Ejaculation is not necessary for transmission to occur, and genital acquisition from direct orogenital contact is possible although rare. Pharyngeal infection following orogenital contact is usually asymptomatic and has been detected in 3% to 6% of individuals in an STI clinic. 18 However, these findings are old and have not been recently challenged. Pharyngeal infection is thought to be transient and does not lead to significant symptoms. 18,19 Anal infection occurs following penetration. Penile rubbing is anecdotally related but no publication reports it. CT can also be transmitted from the genital tract of infected mothers to their newborns. 9
RISK FACTORS
A recent Canadian review of the literature from 1985 to 2000 has shown a potential risk factor for CT infection, found in a diverse group of people, to be young age in females and males. 9 CT was not concentrated in low-income minority core groups with high rates of partner change, unlike gonorrhoea infections. 9 The researchers also found that there was no clear evidence that CT infection was associated with particular types of sex partners (e.g., drug users, sex trade workers, or anonymous partners), contraceptive use, or age at first intercourse. 9
INCUBATION
Symptoms usually begin 1 to 3 weeks after infection, but this period can be much longer in cases of complications. 2o
Number of cases of ST!, Montreal region, 1990-2001
Recent studies conducted by the Montreal Public Health Department have shown the prevalence rate of CT among street youths to be 6.6%.5 This prevalence is significantly higher among women who have had a pregnancy (10.4%) compared to women who have never given birth (3.6%).5 The prevalence rate was 3.8% among women consulted in clinics such as Centre Local de Services Communautaires or private clinics. 5 The prevalence rate was significantly higher among women with a history of abortion (5.1 %) than in women without such a history (2.7%),5 The prevalence of CT in women presenting for
32
Intectlous SWlh\H.
1-
____ 6_ 4
3
-6
11
19961997 1998 1999 ZOOO 2001
Figure I. Reported cases of Chlamydia, Gonorrhea, and Infectious Syphilis in Montreal, 1990-2001 5
Table 1. Reported Cases and Rates* of Genital Chlamydia in Canada, 1991-2002",12
Cases Rate
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
48284 171.7
46365 162.4
44022 152.1
41235 141.0
37551 126.8
34399 114.8
34144 112.7
39034 128.8
42141 138.2
46452 515.1
49880 160.5
56093 179.5
• Rates are per 100 000 population.
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SIGNS AND SYMPTOMS
Up to 50% of men and up to 70% of women infected with Chlamydia have no symptoms. 1O Signs of genital infection are usually subtle in both women and men. 19 The presence of mucopurulent cervicitis is not very specific for cervical infection by CT.21 Figure 2 presents a decision tree for the management of women with abnormal cervical discharge. These women should be tested with the best tests available for CT and Neisseria gonorrhoeae, preferably nucleic acid amplification techniques. 23 Symptomatic infection in women is characterized by genital discharge, abdominal or pelvic pain, burning on urination, and abnormal vaginal bleeding. 19 Signs of infections in men are also subtle. CT infection may cause faint transient urethral watery discharge that is more common in the morning. 19 Symptomatic infection in men is characterized by discharge from the penis, urethral itch, and burning on urination. 19 Symptomatic infection in infants manifests as conjunctivitis, pneumonia, otitis media, and rectal or vaginal complaints, such as discharge. 19 COMPLICATIONS
New data suggest that CT has many deleterious effects on host
•
cell transcription in diverse pathways, which explains the variety of complications accompanying even asymptomatic infections.6 Since so many cases of CT are silent, untreated infection in women may lead to pelvic inflammatory disease (PID).24,25 Indeed, CT may cause as many as 40% of all cases ofPID, which in turn may cause tubal infertility (20%), debilitating chronic pelvic pain (18%), and life-threatening ectopic pregnancy (9%).19 The majority of women with PID will present with symptoms so mild or non-specific that they usually defer seeking medical attention. 18 When present, symptoms may include lower abdominal pain of recent onset, heavy menstruation, intermenstrual or postcoital bleeding, deep dyspareunia, and vaginal discharge that is not readily explained. 19 The signs vary and may include cervical motion tenderness, adnexal tenderness on bimanual exam (with or without a mass), and less frequently, cervicitis and fever. 19 Factors that can aggravate the episode ofPID include use of an intrauterine device, previous PID, pregnancy, and recent upper genital tract manipulation. 19 A negative ultrasound does not rule out a diagnosis ofPID. It has been debated from time to time whether PID is an inadequate term. 19 Recently, the Infectious Diseases Society for Obstetrics and Gynecologf6 approved recommendations that
Abnormal cervical discharge*t
•
~------------------~II~________________~
Presence of factors· that put Abs~neeofJactqts~~t~fpUt .. patients most at risk~patlentSmQ8tltri$k:f::[.·· ..
~
Te" fm gonl~ci "nd chlamyd;,
r
Test for gonococci and chlamydia Wait for result -.
(+)
• Treat immediately for gonococci and chlamydia • Evaluate and treat partners
~
• Treat depending on results • Evaluate and treat partners of positive cases
(-) • No treatment
~
Follow-up visits: • Follow-up should be arranged, but if a recommended treatment is given and taken, symptoms and signs disappear and there is no re-exposure to an untreated partner, repeat diagnostic testing for N. gonorrhoeae and C. trachomatis is not routinely recommended. • If abnormalities persist, consider other diagnosiS (i.e., non-infectious causes). One that is cloudy, yellow. or green. One method to make a diagnosis is a swab test: a swab of endocervical discharge appears green or yellow when held against a white background. A positive swab test in the presence of ahnormal cervical discharge is grounds for presumptive therapy. If found in a low-risk patient who will return for a test result, presumptive treatment can be withheld as the finding is associated with a poor positive predictive value in this population. At risk are sexually active males and females <25 years of age. Those most at risk are contacts to known cases of STD, street involved or substance users, engaging in unprotected sex, with new Of >2 partners in past 6 months, or have previously had STD.
Figure 2. Decision Tree: Abnormal Cervical Discharge 22
the term "upper genital tract infection" be substituted for "PID" and that the criteria for diagnosis include the requirement that the disease involve at least the endometrium and the fallopian tubes, and that the causative agents are major sexually transmitted disease pathogens. In men, CT can lead to epididymitis and, rarely, infertility. The etiologic role of CT in prostatitis is still unclear. Infants born to infected mothers may develop lung infections or, more frequently, sight-threatening eye infections similar to trachoma. 27 Genital chlamydial infection, whether symptomatic or asymptomatic, increases the risk ofHN by a factor of 3 to 5, by enhancing the susceptibility to HN infection if exposed. 27,28 Recent studies have demonstrated that CT infection can act as a co-factor to the human papillomavirus (HPV), increasing both the risk of squamous cell cancer of the cervix and the risk of cancer associated with HPV infection. 29,3o Preliminary data suggest a serious interaction between Herpes simplex virus (HSV) type 2 and cr, where CT, under the influence ofHSV, is changed from the elementary form, which is susceptible to antibiotics, to the reticular form, which is resistant to antibiotics. 3! Confirmation is needed of this alarming finding. PERIOD OF COMMUNICABIUTY
CT infection can persist for years undetected and untreated,24,32 thus asymptomatic carriers act as the major reservoir for the spread of CT. However, the spontaneous clearance rate could be high, challenging the thought that, ifleft untreated, the infection would linger for a long time. 33 SCREENING
Official recommendations for CT screening remain quite broad.!,2 Efforts for more precise screening criteria have been
REPEAT "STI SCREENERS"
Table 2. Criteria for CT Screening' • Age <25 years, if in a reproductive care or STI clinic • Age <25 years with a new sexual partner in the last 2 months • Age <25 years with more than 2 sexual partners in the last year • Age <25 years and has contracted an STI in the last year • • • • • •
largely unsuccessful due to the frequency and widespread nature of CT infection. The classical criteria for CT screening1,5,30,34,35 remain in effect, especially if they are compounded by the characteristics established as criteria for CT screening by the Montreal Public Health Program (Table 2).5 Although systematic or universal screening for CT among all sexually active youths under the age of 25 years is not recommended, screening can occur in particular clinical environments, such as in reproductive care clinics or STI clinics where the prevalence of CT is at its highest. To eliminate the risk of false negative or false positive results, it is recommended to wait 3 weeks after the end of any antibiotic treatment (including single-dose regimens) before assessing cure. Although there is no evidence for this recommendation, it is accepted practice among STI specialists. For utethral and urine tests, it is preferable to wait 1 hour after the last urination before obtaining a specimen for CT testing. In menstruating women, a sample taken from the endocervix can be obtained if bleeding is not too abundant (see Table 3). When menstrual bleeding is substantial, either a urethral sampling or a urine test should be taken, especially if the woman cannot or is unlikely to return for testing. If the specimen is obtained a few days after the sexual contact at risk, the probability of false-negative results will be decreased. No solid data are available regarding the time interval to testing positive after exposute to CT. Thus, if a highrisk person who is regularly exposed to potential infection through unprotected intercourse presents at the clinician's office, it is preferable to perform the test right away even if the person could be considered in a window period. The window period for testing in CT is not very well-defined, but may certainly be shorter than the period considered by many clinicians, due to the much increased sensitivity ofNAATs compared to previously used ELISA tests. Screening at presentation, rather than waiting to be outside a putative window period for incubation, would generate more positive results more rapidly.
Street youths Women requesting an abortion Individuals with multiple sex partners Men who have sex with men Hard drug users Individuals who have had sexual relations with a new partner who has recently been to a country where STI and HIV are highly endemic • Individuals who have had sexual relations with a partner from a country where STI and HIV are highly endemic • Sex trade workers • Individuals who request to be tested, even if they have no evidence or evoked risk factors
Persons presenting for repeated requests for STI screening remain a challenge. It is important for these individuals to
Table 3. Sampling Techniques for Women Sample site
Preferably the endocervix, but urine can be considered appropriate if pelvic examination not possible or acceptable. Vagina or urethra may be sampled in hysterectomized women.
Sample type, storage, and transport
For NAAT tests: secretions obtained on a manufacturer-supplied swab transported at 5 days maximum if at room temperature, or maximum of 7 days if 2°e to 8°C. If possible, at least a few days after intercourse or menses. If risk factors present.
Timing Repeat
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understand that screening is "after the fuct prevention," intended to limit complications and transmission. Some of these individuals adopt the attitude of natural protection after repeated negative screening, and this belief gives them a false sense of security. For these high-risk individuals, the frequency for repeating screening tests is not well-established, but a time frame of 3 to 6 months seems to be accepted.
detecting CT are higher than for any antigen detection tests, such as direct immunofluorescence, non-amplified nucleic tests and EIA techniques (Table 4).5 For medicolegal considerations, only a positive result from an NAAT test confirmed by a second set of primers has value when cell culture is not available. 1 A fluid-based specimen, extracted from the residual liquid taken for liquid-based cervical cytology, can be used for CT testing. 2
SELECTING CANDIDATES FOR TESTING
ANALYZING URINE SAMPLES
Individuals who have repeated STIs or multiple sex partners should be considered for evaluation every 3 to 6 months. The Centers for Disease Control and Prevention recommend that all women be retested 3 to 4 months after CT-positive tests and treatment. 3D Those who have had unprotected sex with someone in any of the risk groups mentioned in Table 2 should have the same screening tests as the person in the group itself 5,34 Pregnant women who have either a risk factor or a partner with a risk factor should also be tested for CT.5,34 Newborns with 1 or both parents with an STI or whose parents are at significant risk for an STI are also candidates for CT testing.
Urine sample tests using NAATs can be applied to test not only genital secretions (from the cervix in women, or from the urethra in both men and women) but also urinary specimens. However, for complete evaluation, a genital and pelvic examination and genital specimen are still the best choice. Urinary sample tests should only be considered when obtaining a genital specimen is not practical or is unacceptable to the patient. The urine test is especially pertinent for men, who are more reluctant to be tested. Optimally, the patient has not urinated for 2 hours before obtaining the first 10 mL of urine. The urine can remain at room temperature for a maximum of 24 hours, but should ideally be refrigerated between 2°C and B°C.
LABORATORY TESTING
Over the last few years, most laboratories in Montreal,5 and presumably throughout Canada, have been offering CT tests by NAAT using the polymerase chain reaction (PCR). This method is commercially available under the name Amplicor and is manufactured and distributed by Roche Diagnostics. Other NAAT methods are also available, such as ligase chain reaction (LCR) or transcription mediated assay (TMA). The LCR test produced by Abbott Laboratories has been temporarily withdrawn from the market due to inconsistency in lots. Non-amplified nucleic acid tests exist, but fare no better than previous enzyme immunoassay (EIA) techniques. The sensitivity (proportion of infected people identified through testing) and specificity (proportion of uninfected people identified through testing as noninfected) ofNAAT in
OTHER POTENTIAL SCREENING SITES
Individuals who participate in oral or anal sex may be interested in testing the anus and throat, however, neither site can be tested using the NAAT. The only appropriate test is a cell culture, with major outer membrane protein stain of direct immunofluorescence. 2 TEST OF CURE
For urethral or endocervical CT infection, repeat testing on follow-up of treatment is not usually recommended. 2 However, it is recommended to repeat the test no more than 3 weeks after treatment if any of the following factors exists: • compliance with treatment is difficult to verifY • the prescribed treatment is not optimal
Table 4. Comparison of CT Test Performances Transport Urine Medicolegal use Availability
NAAT*
Non-Amplified Probe
DFAt
Room temperature Possible Possible Large
Room temperature Possible Not possible Minimal
Room temperature Not possible Not possible Decreasing
Sensitivity, % Genital EIA Genital PCR§ Urinary peR
Room temperature Not adequate Not possible Decreasing
Specificity, %
Men
Women
Men
Women
60.0 99.1 94.4
65.1 96.5 95.1
75-95 98.5 100
95.9 99.4 99.8
* Nucleic acid amplification technique. t Direct fluorescence antibody. ::1= Enzyme immunoassay. § Polymerase chain reaction.
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from sexual relations or use a condom until 7 days after the end of the treatment, even if the treatment was a single dose. 30
• the patient is a child • the patient is a pregnant woman • there is a history of treatment failure
PUBLIC HEALTH DUTIES
TREATMENT UNCOMPLICATED CASES
A recent meta-analysis of the treatment of CT has shown no difference in efficacy between azithromycin and doxycycline for genital chlamydial infections,26 but because of its ease of administration and compliance issues, azithromycin was considered more cost-effective and should be the treatment of choice for uncomplicated cases (Table 5). An asymptomatic partner of an infected person should be given this treatment even in the absence of positive tests. Azithromycin can also be taken in the presence of a health-care worker, confirming compliance to the total I-dose treatment. The treatment of choice for uncomplicated CT infection of the cervix, anus, or urethra in adults and adolescents is azithromycin Ig po in 1 dose. Alternative treatments are doxycycline 100 mg po b.i.d. for 7 days or ofloxacin 300 mg po b.i.d. for7 days. Pregnant women, breastfeeding mothers, and women susceptible to pregnancy or planning a pregnancy should be treated with amoxicillin 500 mg po b.i.d. for 7 days or azithromycin 1 g po in a single dose. Although not actually recommended,36,37 azithromycin is commonly used for treatment in pregnancy, but its safety and efficacy are not well-established. COMPLICATED CASES
People who have complicated cases, such as PID and perihepatitis, should be offered treatment with at least 2 agents because of the usual superinfection occurring with PID. Oral therapy, which is preferred in most cases and should be reassessed within 72 hours, involves cefixime 800 mg po in a single dose plus doxycycline 100 mg b.i.d. for 14 days. Intravenous therapy consists of cefoxitin 2 g every 8 hours plus doxycycline 100 mg IV or po b.i.d., both for at least 48 hours after substantial clinical improvement has occurred, followed by a step-down regimen of cefixime 400 mg po b.i.d. plus doxycycline 100 mg b.i.d. to complete 14 days of therapy. The costs of most of these drugs are covered by provincial or tertitorial health benefit programs and are provided free for both patients and their partners. Patient and partners should abstain
Treatment of infected persons is not complete without adherence to all of the public health regulations pertinent to STIs, including preventive intervention for partners of infected persons (previously known as "partner notification") and public health notification. The Montreal Public Health Direction has established a policy of preventive intervention for the p~rtners of infected persons. s The policy describes the process of notifYing all sexual partners, including sexual contacts of an anonymous or casual nature. The recommended global approach includes identification of sexual partners, location where the partners can be found or contacted, assessment, treatment of sexual partners even in the absence of signs, symptoms, or positive tests, testing when diagnostic resources are not readily accessible, and counselling on prevention measures to reduce the risk of repeat infection among the partners and to avoid spreading the infection in the community. This preventive intervention is recommended even in the case of a clinical syndrome that is compatible with an ST!, such as a clinical diagnosis ofPID, urethritis, mucopurulent cervicitis, or proctitis. INFECTION OF PARTNERS
The infection rate is high among both male and female partners of individuals suffering from an STI, many of whom remain asymptomatic. If patients prefer to personally inform their partners, then at a follow-up visit post-treatment efforts should be made to ensure that the partners have not only been effectively notified but have also been adequately treated. If a woman does not wish to personally notifY her partners, then a third party, such as a physician, a nurse, or a public health professional, should notifY the partners without revealing the woman's identity. The information needed to contact the partner includes name, sex, address, telephone numbers (home and work), date and type of exposure, age or date of birth, and place of work or study. In some cities, such as Montreal, public health authorities would consider providing special assistance to the physician or the patient in the circumstances listed in Table 6.
Table 5. Treatment Options Treatment of Choice Azithromycin 1 gpo b.i.d. in 1 dose
Alternative Treatments
Treatments Recommended for Pregnant or Breastfeeding Women
Doxycycline 100 mg po b.i.d. x 7 days
Amoxicillin 500 mg po t.i.d. x 7 days
or
or
Ofloxacin 300 mg po b.i.d. x 7 days
Azithromycin 1 g po in 1 dose
JOGC _JUNE 2004
according to national standards, and evaluate and treat all sexual partners without delay.
DELAY FOR PREVENTIVE INTERVENTION TREATMENT
Even with a delay of 60 days, it is still appropriate to contact and treat all partners of persons with CT infections confirmed by a laboratory test. In addition, it is also appropriate to contact, test, and treat all partners of persons with CT-compatible syndromes, including PID, even in the absence of positive test results. This treatment approach applies to all sexual partners during the 60 days prior to the patient's positive diagnosis if the patient was symptomatic, or to the screening test if the patient was asymptomatic. If the patient who tests positive had no partner during this period, then the most recent partner is contacted. in the case of a newborn, the mother and her sexual partner or partners should be assessed. 5
CT infections are reportable conditions in Canada. More than a bureaucratic gesture, this notification helps public health authorities to track trends and allocate resources adequately. Without proper reponing by physicians, adequate resources will not be allocated to address the current increase in the incidence or prevalence rates of CT. CONCLUSIONS
Chlamydia trachomatis infection rates are increasing at an alarming pace. As CT can cause severe reproductive complications, particularly in women, reproductive-care providers should promote the adoption of safer sexual practices, recognize the signs, symptoms, and risk factors of CT, perform the appropriate screening and diagnostic tests, treat the infected individual Table 6. Circumstances for Special Assistance in Contacting Sexual PartnersS When the woman has had 2 or more partners during the infection period
•
is reluctant to personally inform a particular partner
• fears violence or reprisals •
is suffering from a pelvic inflammatory disease (pI D)
•
has suffered from repeated sexually transmitted infections (5Tls)
•
has undergone several abortions
•
has been exposed through sexual abuse
•
is younger than 20 years of age
When the partner •
is a casual or occasional partner
• appears to playa key role in the transmission process •
appears to be the source of the patient's infection
•
also has several partners
•
is difficult to locate
•
is likely to be unaware of the exposure
•
is pregnant
•
is younger than 20 years of age
The author would like to thank the Montreal Public Health authorities, especially Dr John Cars ley, Dr Gilles Lambert, Dr Monique Letellier, Dr Jean Cloutier, and Mr Blaise Lefebvre, whose work has formed the basis for this review. The author would also like to thank Dr Monique Letellier for her comments on the draft of this article, and Mme Manon Hudson for her assistance in the production of the manuscript.
Ifyou are interested in reviewing and completing case exercises on Chlamydia trachomatis, please visitwww.sogc.org andfollow the link to the e-learning modules.
PUBLIC HEALTH NOTIFICATION
•
ACKNOWLEDGEMENTS
lOGe
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2004
14. Direction de sante publique de Montreal. Infection genitale a Chlamydia trachomatis (fin de la periode 04-2004). Available at. Accessed May 16,2004. 15. Internet use and early syphilis infection among men who have sex with men - San Francisco, California, 1999-2003 MMWR Morb Mortal Wkly Rep. 2003 Dec 19;52(50): 1229-32. 16. Bellis MA, Hughes K,Thomson R, Bennett A. Sexual behaviour of young people in international tourist resorts. Sex Transm Infect 2004 Feb;80( I):43-7. 17. Henricksen K. Harm reduction in the rave community. Focus 2000 Mar; I 5(4): 1-4. 18. Jones RB, Rabinovitch RA, Katz B, Batteiger BE, Quinn RS,Terho P, et al. Chlamydia trachomatis in the pharynx and rectum of heterosexual patients at risk for genital infection. Ann Intern Med 1985; I02:757-62. 19. Stamm WE. Chlamydia trachomatis infections of the adults. In: Holmes KK, Sparling F, Mardh PA, Lemon SM, Stamm WE, Piot P, et aI., editors. Sexually transmitted diseases. 3rd ed. New York: McGraw-Hili; 1999. p.407-9. 20. Peipert JF. Genital chlamydial infections. N Engl J Med 2003;349(25): 2424-30. 21. Peeling RW, Louie TL, Steben M, Louie R, Dillon E, Champoux-Hamel C, et al. Effectiveness of a point-of-care test for the diagnosis of Chlamydia trachomatis in women presenting for voluntary termination of pregnancy. Poster 0706, International Society for STD Research, Ottawa,July 2003. Available at . Accessed May 16, 2004. 22. Health Canada. Highlights - 1998 edition of the Canadian STD guidelines. Available at . Accessed May 16,2004. 23. Berman S. Resurgence of syphilis in the United States. Poster 0314, International Society for STD Research, Ottawa, July 2003. Available at . Accessed May 16,2004. 24. Rees E.Treatment of pelvic inflammatory disease. Am J Obstet Gynecol 1980; 138: I042-7. 25. Stamm WE, Guinan ME, Johnson C, Starcher T, Holmes KK, McCormack WM. Effect of treatment regimens for Neisseria
gonorrhoeae on simultaneous infection with Chlamydia Trachomatis. N Engl J Med 1984;310:545-9. 26. Monif GRG. "Pelvic inflammatory disease" redefined. Infect Med 200 I; 18(4): 190-3. 27. Hammerschlag MR. Chlamydia Trachomatis infections in infants and children. In: Holmes KK, Sparling F, Mardh PA, Lemon SM, Stamm WE, Piot P, et aI., editors. Sexually transmitted diseases. 3rd ed. New York: McGraw-Hili; 1999. p. 1155. 28. Hicks D. Complications of Chlamydia Trachomatis infection in men. In: International handbook of Chlamydia. Haslemere (Surrey): Euromed Communications Ltd; 200 I. p. 71. 29. Sellors J, Howard M, Pickard L,Jang D, Mahony J, Chernesky M. Chlamydial cervicitis: testing the practice guidelines for presumptive diagnosis. CMAJ 1998;158:41-6. 30. Sexually transmitted diseases treatment guidelines 2002. Centers for Disease Control and Prevention. MMWR Recomm Rep 2002;5 I (RR-6):1-78. 31. Schachter J. Biology of Chlamydia trachomatis. In: Holmes KK, Sparling F, Mardh PA, Lemon SM, Stamm WE, Piot P, et al., editors. Sexually transmitted diseases. New York: McGraw-Hili; 1999. p. 391-405. 32. Westrom L,Joesoef R, Reynolds G, Hagdu A,Thompson SE. Pelvic inflammatory disease and fertility: a cohort study of 1,844 women with laparoscopically verified disease and 657 control women with normal laparoscopy results. Sex Transm Dis 1992; 19: 185-92. 33. Morre SA, van den Brule AJC, Rozendaal L, Boeke AJP,Voorhorst FJ, de Blok S, et al.The natural course of asymptomatic Chlamydia trachomatis infection: 45% clearance and no development of clinical PID after one-year follow-up.lnt J STD AIDS 2002; 13 (Suppl 2): 12-8. 34. Comite consultatif MTS. Recommandations de depistage des MTS. MSSS;2000. 35. U.S. Preventive Services Task Force. Screening for Chlamydial infection: recommendations and rationale. Am J Prev Med 200 I;20(3 Suppl):90-4. 36. Adair CD, Gubter M, Stoval TG, McKelroy G,Veilie JC, Ernest JM. Chlamydia in pregnancy: a randomized trial of azithromycin and erithromycin. Obstet Gynecol 1998;91: I65-a. 37. Wehbeh HA, Ruggeirio RM, Shahem S, Lopez G, AliY. Single-dose azithromycin for Chlamydia in pregnant women.J Reprod Med 1998;43:509-14.
JOGe _JUNE 2004
Abstract: The objective of the review is to alert reproductive-care providers to the unexpected resurgence of Chlamydia infections and to new findings related to complications associated with Chlamydia infection. Data sources consisted of national and local guidelines and literature searches of MEDLINE with the heading Chlamydia infections 2002 and 2003. The complications of Chlamydia infections are considered to be longterm, and may include debilitating pain, infertility, tubal pregnancy, cancer, and HIV infection. Only a strong diseasemanagement response from reproductive-care providers, using new diagnostic techniques and simpler treatment regimens, as well as a strong public health reaction, will be effective to limit the scourges of Chlamydia infection in the female population. Resume: La presente analyse a pour objectif d'eveiller I'attention des fournisseurs de soins genesiques sur la recrudescence inatten due des infections a Chlamydia, ainsi que sur les nouveaux resultats de recherche lies aux complications associees aces infections. Des lignes directrices nationales et locales et des recherches documentaires dans MEDLINE (en utilisant les mots cles Chlamydia infections 2002 and 2003) ont ete utilisees a titre de sources de donnees. Les complications des infections a Chlamydia sont considerees comme etant a long terme et peuvent inclure la douleur debilitante, I'infertilite, la grossesse tubaire, Ie cancer et I'infection au VIH. Seule une solide gestion therapeutique de la part des fournisseurs de soins genesiques (faisant appel a de nouvelles techniques diagnostiques et a des schemas therapeutiques simplifies), conjuguee a une forte reaction de la part du secteur de la sante publique, parviendra a endiguer Ie fleau de I'infection a Chlamydia au sein de la population feminine.
J Obstet
INTRODUCTION
Genital Chlamydia trachomatis (CT) is a sexually transmitted infection (511) caused by the bacterium Chlamydia trachomatis. Females are disproportionately affected by the complications of this infection. 1,2 Optimism about the decreasing rates of CT flourished3 following the introduction of nucleic acid amplification techniques (NMTs) for diagnosis and screening purposes, and the availability of a simple unique oral dose of azithromycin for the treatment of uncomplicated urogenital infection. 4 This optimism has subsequently abated as new risk factors, as well as the re-emergence of old risk factors, have helped CT rebound to heights not seen for more than a decade. 5 Confronted with this worrisome resurgence, Montreal Public Health authorities released a plan of action 5 requiring "an energetic and coordinated response" from all reproductive-care providers to: • promote the adoption of safer sexual practices, • recognize the signs and symptoms of CT infections and perform appropriate diagnostic tests, • recognize, in the absence of signs and symptoms, the presence of risk factors, and perform appropriate screening tests, • treat infected people according to national standards, and • evaluate and treat all the sexual partners of infected persons within the 60-day recommended window period without delay.s New data are emerging about the deleterious effect that CT has on functions of infected cells, making this review necessary.6
Gynaecol Can 2004;26(6):552-9. METHODS
KeyWords Chlamydia trachomatis; Chlamydia infections; sexually transmitted diseases, bacterial - prevention and control; communicable disease control; contact tracing Competing interests: None declared. Received on October 14, 2003 Revised and accepted on April 9, 2004
Data sources consisted of national and local guidelines, and literature searches of MEDLINE using the key words" Chlamydia trachomatis," "Chlamydia infection," "sexually transmitted infection - bacterial," "prevention and control," "communicable disease control," and "contact tracing." EPIDEMIOLOGY
According to Health Canada, the estimated worldwide annual JOGC _JUNE 2004
termination of pregnancy in Lasalle, Quebec, and in Calgary, Alberta, was 8.5%, with bacterial vaginosis, casual sex, history of CT, and history of STI being significant risk factors. 5 New risk factors have recently emerged, such as sexual encounters organized through chat-rooms,15 casual sex during travel abroad,16 and rave parties. 17 These factors have all been associated with high-risk sexual activities in all patient groups, but except for their association with the acquisition of syphilis in gay men, these new risk factors have not yet been associated with higher rates ofSTIs in heterosexual persons. 6
incidence of CT cases in 1995 was 89 million, the greatest number being in Asia, followed by sub-Saharan Mrica. 7 In the United States, the reported rates ofCT infection have risen from 51 per 100 000 persons in 1987 to 278 per 100 000 persons in 2001. 8- 10 In Canada, CT is the most frequently reported bacterial infection (Table 1).3 Rates for women are at least 2 to 7 times higher in the age populations most at risk for CT complications when compared to risks for men of the same age group. 13 In Montreal, the number of reported cases of Chlamydia infection decreased by 65% from 1990 to 1996, but increased by 75% from 1996 to 2001 (Figure 1). Women continue to be the most affected (70% of all cases), especially those aged 15 to 24 years. The incidence rate in Montreal, in 2003, was 1433.2 cases per 100 000 among 15- to 19-year-old women, and 1871.2 cases per 100 000 among those aged 20 to 24 years. 14 These rates are 2 to 3 times higher than the target of 500 per 100 000 set for Canadian women in these age groups for the year 2000. 5 The incidence of Neisseria gonorrhoeae, Treponema pallidum, and CT infection, the 3 most common STIs, is increasing in most large cities. However, Neisseria gonorrhoeae and Treponema pallidum infections are diagnosed mostly in homosexual men, while CT is seen mostly in heterosexual men and women.
CUNICAL PRESENTATIONS TRANSMISSION
Genital CT is transmirted through direct genital-to-genital contact with an infected individual, who is most frequently asymptomatic. 8 Ejaculation is not necessary for transmission to occur, and genital acquisition from direct orogenital contact is possible although rare. Pharyngeal infection following orogenital contact is usually asymptomatic and has been detected in 3% to 6% of individuals in an STI clinic. 18 However, these findings are old and have not been recently challenged. Pharyngeal infection is thought to be transient and does not lead to significant symptoms. 18,19 Anal infection occurs following penetration. Penile rubbing is anecdotally related but no publication reports it. CT can also be transmitted from the genital tract of infected mothers to their newborns. 9
RISK FACTORS
A recent Canadian review of the literature from 1985 to 2000 has shown a potential risk factor for CT infection, found in a diverse group of people, to be young age in females and males. 9 CT was not concentrated in low-income minority core groups with high rates of partner change, unlike gonorrhoea infections. 9 The researchers also found that there was no clear evidence that CT infection was associated with particular types of sex partners (e.g., drug users, sex trade workers, or anonymous partners), contraceptive use, or age at first intercourse. 9
INCUBATION
Symptoms usually begin 1 to 3 weeks after infection, but this period can be much longer in cases of complications. 2o
Number of cases of ST!, Montreal region, 1990-2001
Recent studies conducted by the Montreal Public Health Department have shown the prevalence rate of CT among street youths to be 6.6%.5 This prevalence is significantly higher among women who have had a pregnancy (10.4%) compared to women who have never given birth (3.6%).5 The prevalence rate was 3.8% among women consulted in clinics such as Centre Local de Services Communautaires or private clinics. 5 The prevalence rate was significantly higher among women with a history of abortion (5.1 %) than in women without such a history (2.7%),5 The prevalence of CT in women presenting for
32
Intectlous SWlh\H.
1-
____ 6_ 4
3
-6
11
19961997 1998 1999 ZOOO 2001
Figure I. Reported cases of Chlamydia, Gonorrhea, and Infectious Syphilis in Montreal, 1990-2001 5
Table 1. Reported Cases and Rates* of Genital Chlamydia in Canada, 1991-2002",12
Cases Rate
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
48284 171.7
46365 162.4
44022 152.1
41235 141.0
37551 126.8
34399 114.8
34144 112.7
39034 128.8
42141 138.2
46452 515.1
49880 160.5
56093 179.5
• Rates are per 100 000 population.
JOGC _JUNE 2004
SIGNS AND SYMPTOMS
Up to 50% of men and up to 70% of women infected with Chlamydia have no symptoms. 1O Signs of genital infection are usually subtle in both women and men. 19 The presence of mucopurulent cervicitis is not very specific for cervical infection by CT.21 Figure 2 presents a decision tree for the management of women with abnormal cervical discharge. These women should be tested with the best tests available for CT and Neisseria gonorrhoeae, preferably nucleic acid amplification techniques. 23 Symptomatic infection in women is characterized by genital discharge, abdominal or pelvic pain, burning on urination, and abnormal vaginal bleeding. 19 Signs of infections in men are also subtle. CT infection may cause faint transient urethral watery discharge that is more common in the morning. 19 Symptomatic infection in men is characterized by discharge from the penis, urethral itch, and burning on urination. 19 Symptomatic infection in infants manifests as conjunctivitis, pneumonia, otitis media, and rectal or vaginal complaints, such as discharge. 19 COMPLICATIONS
New data suggest that CT has many deleterious effects on host
•
cell transcription in diverse pathways, which explains the variety of complications accompanying even asymptomatic infections.6 Since so many cases of CT are silent, untreated infection in women may lead to pelvic inflammatory disease (PID).24,25 Indeed, CT may cause as many as 40% of all cases ofPID, which in turn may cause tubal infertility (20%), debilitating chronic pelvic pain (18%), and life-threatening ectopic pregnancy (9%).19 The majority of women with PID will present with symptoms so mild or non-specific that they usually defer seeking medical attention. 18 When present, symptoms may include lower abdominal pain of recent onset, heavy menstruation, intermenstrual or postcoital bleeding, deep dyspareunia, and vaginal discharge that is not readily explained. 19 The signs vary and may include cervical motion tenderness, adnexal tenderness on bimanual exam (with or without a mass), and less frequently, cervicitis and fever. 19 Factors that can aggravate the episode ofPID include use of an intrauterine device, previous PID, pregnancy, and recent upper genital tract manipulation. 19 A negative ultrasound does not rule out a diagnosis ofPID. It has been debated from time to time whether PID is an inadequate term. 19 Recently, the Infectious Diseases Society for Obstetrics and Gynecologf6 approved recommendations that
Abnormal cervical discharge*t
•
~------------------~II~________________~
Presence of factors· that put Abs~neeofJactqts~~t~fpUt .. patients most at risk~patlentSmQ8tltri$k:f::[.·· ..
~
Te" fm gonl~ci "nd chlamyd;,
r
Test for gonococci and chlamydia Wait for result -.
(+)
• Treat immediately for gonococci and chlamydia • Evaluate and treat partners
~
• Treat depending on results • Evaluate and treat partners of positive cases
(-) • No treatment
~
Follow-up visits: • Follow-up should be arranged, but if a recommended treatment is given and taken, symptoms and signs disappear and there is no re-exposure to an untreated partner, repeat diagnostic testing for N. gonorrhoeae and C. trachomatis is not routinely recommended. • If abnormalities persist, consider other diagnosiS (i.e., non-infectious causes). One that is cloudy, yellow. or green. One method to make a diagnosis is a swab test: a swab of endocervical discharge appears green or yellow when held against a white background. A positive swab test in the presence of ahnormal cervical discharge is grounds for presumptive therapy. If found in a low-risk patient who will return for a test result, presumptive treatment can be withheld as the finding is associated with a poor positive predictive value in this population. At risk are sexually active males and females <25 years of age. Those most at risk are contacts to known cases of STD, street involved or substance users, engaging in unprotected sex, with new Of >2 partners in past 6 months, or have previously had STD.
Figure 2. Decision Tree: Abnormal Cervical Discharge 22
the term "upper genital tract infection" be substituted for "PID" and that the criteria for diagnosis include the requirement that the disease involve at least the endometrium and the fallopian tubes, and that the causative agents are major sexually transmitted disease pathogens. In men, CT can lead to epididymitis and, rarely, infertility. The etiologic role of CT in prostatitis is still unclear. Infants born to infected mothers may develop lung infections or, more frequently, sight-threatening eye infections similar to trachoma. 27 Genital chlamydial infection, whether symptomatic or asymptomatic, increases the risk ofHN by a factor of 3 to 5, by enhancing the susceptibility to HN infection if exposed. 27,28 Recent studies have demonstrated that CT infection can act as a co-factor to the human papillomavirus (HPV), increasing both the risk of squamous cell cancer of the cervix and the risk of cancer associated with HPV infection. 29,3o Preliminary data suggest a serious interaction between Herpes simplex virus (HSV) type 2 and cr, where CT, under the influence ofHSV, is changed from the elementary form, which is susceptible to antibiotics, to the reticular form, which is resistant to antibiotics. 3! Confirmation is needed of this alarming finding. PERIOD OF COMMUNICABIUTY
CT infection can persist for years undetected and untreated,24,32 thus asymptomatic carriers act as the major reservoir for the spread of CT. However, the spontaneous clearance rate could be high, challenging the thought that, ifleft untreated, the infection would linger for a long time. 33 SCREENING
Official recommendations for CT screening remain quite broad.!,2 Efforts for more precise screening criteria have been
REPEAT "STI SCREENERS"
Table 2. Criteria for CT Screening' • Age <25 years, if in a reproductive care or STI clinic • Age <25 years with a new sexual partner in the last 2 months • Age <25 years with more than 2 sexual partners in the last year • Age <25 years and has contracted an STI in the last year • • • • • •
largely unsuccessful due to the frequency and widespread nature of CT infection. The classical criteria for CT screening1,5,30,34,35 remain in effect, especially if they are compounded by the characteristics established as criteria for CT screening by the Montreal Public Health Program (Table 2).5 Although systematic or universal screening for CT among all sexually active youths under the age of 25 years is not recommended, screening can occur in particular clinical environments, such as in reproductive care clinics or STI clinics where the prevalence of CT is at its highest. To eliminate the risk of false negative or false positive results, it is recommended to wait 3 weeks after the end of any antibiotic treatment (including single-dose regimens) before assessing cure. Although there is no evidence for this recommendation, it is accepted practice among STI specialists. For utethral and urine tests, it is preferable to wait 1 hour after the last urination before obtaining a specimen for CT testing. In menstruating women, a sample taken from the endocervix can be obtained if bleeding is not too abundant (see Table 3). When menstrual bleeding is substantial, either a urethral sampling or a urine test should be taken, especially if the woman cannot or is unlikely to return for testing. If the specimen is obtained a few days after the sexual contact at risk, the probability of false-negative results will be decreased. No solid data are available regarding the time interval to testing positive after exposute to CT. Thus, if a highrisk person who is regularly exposed to potential infection through unprotected intercourse presents at the clinician's office, it is preferable to perform the test right away even if the person could be considered in a window period. The window period for testing in CT is not very well-defined, but may certainly be shorter than the period considered by many clinicians, due to the much increased sensitivity ofNAATs compared to previously used ELISA tests. Screening at presentation, rather than waiting to be outside a putative window period for incubation, would generate more positive results more rapidly.
Street youths Women requesting an abortion Individuals with multiple sex partners Men who have sex with men Hard drug users Individuals who have had sexual relations with a new partner who has recently been to a country where STI and HIV are highly endemic • Individuals who have had sexual relations with a partner from a country where STI and HIV are highly endemic • Sex trade workers • Individuals who request to be tested, even if they have no evidence or evoked risk factors
Persons presenting for repeated requests for STI screening remain a challenge. It is important for these individuals to
Table 3. Sampling Techniques for Women Sample site
Preferably the endocervix, but urine can be considered appropriate if pelvic examination not possible or acceptable. Vagina or urethra may be sampled in hysterectomized women.
Sample type, storage, and transport
For NAAT tests: secretions obtained on a manufacturer-supplied swab transported at 5 days maximum if at room temperature, or maximum of 7 days if 2°e to 8°C. If possible, at least a few days after intercourse or menses. If risk factors present.
Timing Repeat
JOGC _JUNE 2004
understand that screening is "after the fuct prevention," intended to limit complications and transmission. Some of these individuals adopt the attitude of natural protection after repeated negative screening, and this belief gives them a false sense of security. For these high-risk individuals, the frequency for repeating screening tests is not well-established, but a time frame of 3 to 6 months seems to be accepted.
detecting CT are higher than for any antigen detection tests, such as direct immunofluorescence, non-amplified nucleic tests and EIA techniques (Table 4).5 For medicolegal considerations, only a positive result from an NAAT test confirmed by a second set of primers has value when cell culture is not available. 1 A fluid-based specimen, extracted from the residual liquid taken for liquid-based cervical cytology, can be used for CT testing. 2
SELECTING CANDIDATES FOR TESTING
ANALYZING URINE SAMPLES
Individuals who have repeated STIs or multiple sex partners should be considered for evaluation every 3 to 6 months. The Centers for Disease Control and Prevention recommend that all women be retested 3 to 4 months after CT-positive tests and treatment. 3D Those who have had unprotected sex with someone in any of the risk groups mentioned in Table 2 should have the same screening tests as the person in the group itself 5,34 Pregnant women who have either a risk factor or a partner with a risk factor should also be tested for CT.5,34 Newborns with 1 or both parents with an STI or whose parents are at significant risk for an STI are also candidates for CT testing.
Urine sample tests using NAATs can be applied to test not only genital secretions (from the cervix in women, or from the urethra in both men and women) but also urinary specimens. However, for complete evaluation, a genital and pelvic examination and genital specimen are still the best choice. Urinary sample tests should only be considered when obtaining a genital specimen is not practical or is unacceptable to the patient. The urine test is especially pertinent for men, who are more reluctant to be tested. Optimally, the patient has not urinated for 2 hours before obtaining the first 10 mL of urine. The urine can remain at room temperature for a maximum of 24 hours, but should ideally be refrigerated between 2°C and B°C.
LABORATORY TESTING
Over the last few years, most laboratories in Montreal,5 and presumably throughout Canada, have been offering CT tests by NAAT using the polymerase chain reaction (PCR). This method is commercially available under the name Amplicor and is manufactured and distributed by Roche Diagnostics. Other NAAT methods are also available, such as ligase chain reaction (LCR) or transcription mediated assay (TMA). The LCR test produced by Abbott Laboratories has been temporarily withdrawn from the market due to inconsistency in lots. Non-amplified nucleic acid tests exist, but fare no better than previous enzyme immunoassay (EIA) techniques. The sensitivity (proportion of infected people identified through testing) and specificity (proportion of uninfected people identified through testing as noninfected) ofNAAT in
OTHER POTENTIAL SCREENING SITES
Individuals who participate in oral or anal sex may be interested in testing the anus and throat, however, neither site can be tested using the NAAT. The only appropriate test is a cell culture, with major outer membrane protein stain of direct immunofluorescence. 2 TEST OF CURE
For urethral or endocervical CT infection, repeat testing on follow-up of treatment is not usually recommended. 2 However, it is recommended to repeat the test no more than 3 weeks after treatment if any of the following factors exists: • compliance with treatment is difficult to verifY • the prescribed treatment is not optimal
Table 4. Comparison of CT Test Performances Transport Urine Medicolegal use Availability
NAAT*
Non-Amplified Probe
DFAt
Room temperature Possible Possible Large
Room temperature Possible Not possible Minimal
Room temperature Not possible Not possible Decreasing
Sensitivity, % Genital EIA Genital PCR§ Urinary peR
Room temperature Not adequate Not possible Decreasing
Specificity, %
Men
Women
Men
Women
60.0 99.1 94.4
65.1 96.5 95.1
75-95 98.5 100
95.9 99.4 99.8
* Nucleic acid amplification technique. t Direct fluorescence antibody. ::1= Enzyme immunoassay. § Polymerase chain reaction.
JOGe
JUNE 2004
from sexual relations or use a condom until 7 days after the end of the treatment, even if the treatment was a single dose. 30
• the patient is a child • the patient is a pregnant woman • there is a history of treatment failure
PUBLIC HEALTH DUTIES
TREATMENT UNCOMPLICATED CASES
A recent meta-analysis of the treatment of CT has shown no difference in efficacy between azithromycin and doxycycline for genital chlamydial infections,26 but because of its ease of administration and compliance issues, azithromycin was considered more cost-effective and should be the treatment of choice for uncomplicated cases (Table 5). An asymptomatic partner of an infected person should be given this treatment even in the absence of positive tests. Azithromycin can also be taken in the presence of a health-care worker, confirming compliance to the total I-dose treatment. The treatment of choice for uncomplicated CT infection of the cervix, anus, or urethra in adults and adolescents is azithromycin Ig po in 1 dose. Alternative treatments are doxycycline 100 mg po b.i.d. for 7 days or ofloxacin 300 mg po b.i.d. for7 days. Pregnant women, breastfeeding mothers, and women susceptible to pregnancy or planning a pregnancy should be treated with amoxicillin 500 mg po b.i.d. for 7 days or azithromycin 1 g po in a single dose. Although not actually recommended,36,37 azithromycin is commonly used for treatment in pregnancy, but its safety and efficacy are not well-established. COMPLICATED CASES
People who have complicated cases, such as PID and perihepatitis, should be offered treatment with at least 2 agents because of the usual superinfection occurring with PID. Oral therapy, which is preferred in most cases and should be reassessed within 72 hours, involves cefixime 800 mg po in a single dose plus doxycycline 100 mg b.i.d. for 14 days. Intravenous therapy consists of cefoxitin 2 g every 8 hours plus doxycycline 100 mg IV or po b.i.d., both for at least 48 hours after substantial clinical improvement has occurred, followed by a step-down regimen of cefixime 400 mg po b.i.d. plus doxycycline 100 mg b.i.d. to complete 14 days of therapy. The costs of most of these drugs are covered by provincial or tertitorial health benefit programs and are provided free for both patients and their partners. Patient and partners should abstain
Treatment of infected persons is not complete without adherence to all of the public health regulations pertinent to STIs, including preventive intervention for partners of infected persons (previously known as "partner notification") and public health notification. The Montreal Public Health Direction has established a policy of preventive intervention for the p~rtners of infected persons. s The policy describes the process of notifYing all sexual partners, including sexual contacts of an anonymous or casual nature. The recommended global approach includes identification of sexual partners, location where the partners can be found or contacted, assessment, treatment of sexual partners even in the absence of signs, symptoms, or positive tests, testing when diagnostic resources are not readily accessible, and counselling on prevention measures to reduce the risk of repeat infection among the partners and to avoid spreading the infection in the community. This preventive intervention is recommended even in the case of a clinical syndrome that is compatible with an ST!, such as a clinical diagnosis ofPID, urethritis, mucopurulent cervicitis, or proctitis. INFECTION OF PARTNERS
The infection rate is high among both male and female partners of individuals suffering from an STI, many of whom remain asymptomatic. If patients prefer to personally inform their partners, then at a follow-up visit post-treatment efforts should be made to ensure that the partners have not only been effectively notified but have also been adequately treated. If a woman does not wish to personally notifY her partners, then a third party, such as a physician, a nurse, or a public health professional, should notifY the partners without revealing the woman's identity. The information needed to contact the partner includes name, sex, address, telephone numbers (home and work), date and type of exposure, age or date of birth, and place of work or study. In some cities, such as Montreal, public health authorities would consider providing special assistance to the physician or the patient in the circumstances listed in Table 6.
Table 5. Treatment Options Treatment of Choice Azithromycin 1 gpo b.i.d. in 1 dose
Alternative Treatments
Treatments Recommended for Pregnant or Breastfeeding Women
Doxycycline 100 mg po b.i.d. x 7 days
Amoxicillin 500 mg po t.i.d. x 7 days
or
or
Ofloxacin 300 mg po b.i.d. x 7 days
Azithromycin 1 g po in 1 dose
JOGC _JUNE 2004
according to national standards, and evaluate and treat all sexual partners without delay.
DELAY FOR PREVENTIVE INTERVENTION TREATMENT
Even with a delay of 60 days, it is still appropriate to contact and treat all partners of persons with CT infections confirmed by a laboratory test. In addition, it is also appropriate to contact, test, and treat all partners of persons with CT-compatible syndromes, including PID, even in the absence of positive test results. This treatment approach applies to all sexual partners during the 60 days prior to the patient's positive diagnosis if the patient was symptomatic, or to the screening test if the patient was asymptomatic. If the patient who tests positive had no partner during this period, then the most recent partner is contacted. in the case of a newborn, the mother and her sexual partner or partners should be assessed. 5
CT infections are reportable conditions in Canada. More than a bureaucratic gesture, this notification helps public health authorities to track trends and allocate resources adequately. Without proper reponing by physicians, adequate resources will not be allocated to address the current increase in the incidence or prevalence rates of CT. CONCLUSIONS
Chlamydia trachomatis infection rates are increasing at an alarming pace. As CT can cause severe reproductive complications, particularly in women, reproductive-care providers should promote the adoption of safer sexual practices, recognize the signs, symptoms, and risk factors of CT, perform the appropriate screening and diagnostic tests, treat the infected individual Table 6. Circumstances for Special Assistance in Contacting Sexual PartnersS When the woman has had 2 or more partners during the infection period
•
is reluctant to personally inform a particular partner
• fears violence or reprisals •
is suffering from a pelvic inflammatory disease (pI D)
•
has suffered from repeated sexually transmitted infections (5Tls)
•
has undergone several abortions
•
has been exposed through sexual abuse
•
is younger than 20 years of age
When the partner •
is a casual or occasional partner
• appears to playa key role in the transmission process •
appears to be the source of the patient's infection
•
also has several partners
•
is difficult to locate
•
is likely to be unaware of the exposure
•
is pregnant
•
is younger than 20 years of age
The author would like to thank the Montreal Public Health authorities, especially Dr John Cars ley, Dr Gilles Lambert, Dr Monique Letellier, Dr Jean Cloutier, and Mr Blaise Lefebvre, whose work has formed the basis for this review. The author would also like to thank Dr Monique Letellier for her comments on the draft of this article, and Mme Manon Hudson for her assistance in the production of the manuscript.
Ifyou are interested in reviewing and completing case exercises on Chlamydia trachomatis, please visitwww.sogc.org andfollow the link to the e-learning modules.
PUBLIC HEALTH NOTIFICATION
•
ACKNOWLEDGEMENTS
lOGe
REFERENCES I. Health Canada. STD treatment guidelines 1998 edition. Available at
2004
14. Direction de sante publique de Montreal. Infection genitale a Chlamydia trachomatis (fin de la periode 04-2004). Available at
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