Management of Women With Cervicitis

Management of Women with Cervicitis
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Oxford Journals
Medicine
Clinical Infectious Diseases
Volume 44, Issue Supplement 3
Pp. S102-S110.
Clinical Infectious Diseases

cid.oxfordjournals.org Clin Infect Dis. (2007) 44 (Supplement 3): S102-S110. doi: 10.1086/511423

Jeanne M. Marrazzo1 and David H. Martin2
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Author Affiliations
Reprints or correspondence: Dr. Jeanne M. Marrazzo, Harborview Medical Center, Div. of Infectious Diseases, 325 Ninth Ave., Mailbox 359931, Seattle, WA 98104 (jmm2@u.washington.edu).
Abstract In the past several years, the collective understanding of cervicitis has extended beyond the recognition of Chlamydia trachomatis and Neisseria gonorrhoeae as the prime etiologic suspects. Trichomonas vaginalis and herpes simplex virus cause cervicitis, and both Mycoplasma genitalium and bacterial vaginosis have emerged as new candidate etiologic agents or conditions. However, major gaps in our knowledge of this common condition remain. Putative etiologic agents have not been identified in many women with cervicitis. Moreover, cervicitis occurs in a relatively small proportion of women with chlamydia or gonorrhea. Finally, scant research has addressed the clinical response of nonchlamydial and nongonococcal cervicitis to antibiotic therapy, and there are no data on the benefit of sex partner treatment for such women. New research into the etiology, immunology, and natural history of this common condition is needed, especially in view of the well-established links between cervicitis and an increased risk of upper genital tract infection and human immunodeficiency virus type 1 acquisition.
In a landmark study published in 1984, Brunham et al. [1, p. 1] recognized the clinical syndrome of cervicitis as the ignored counterpart in women of urethritis in men. These observations, along with those made earlier by Elizabeth Rees and colleagues in the 1970s [2], set the stage for research into the etiology and management of the syndrome of clinically evident cervical inflammation. The term mucopurulent cervicitis arose from these authors' observation that most women with the sexually transmitted diseases (STDs) that caused cervicitis in those studies (namely, Chlamydia trachomatis infection and Neisseria gonorrhoeae infection) displayed endocervical mucopurulent discharge. Despite increasing documentation during the ensuing decades that easily induced endocervical bleeding (sometimes referred to as friability) was equally, if not more, common among women infected with these pathogens, use of the term mucopurulent has persisted. Because this terminology is essentially inaccurate and confusing, the most salient change in the 2006 STD treatment guidelines is the adoption of the term cervicitis in place of mucopurulent cervicitis [3]. Although few population-based data are available to estimate the true prevalence of cervicitis, it appears to be an exceedingly common finding
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among women and is seen in a wide variety of clinical settings. It is important to emphasize that there is no consensus definition for cervicitis as a research outcome. This has led to a literature that is difficult to interpret and to findings that may not necessarily be generalizable. At the most basic level, many studies have not distinguished between the presence of signs in the endocervical canal and those at the ectocervix. These epithelia differ not only in the organisms they host but also in endogenous defense mechanisms, responsiveness to hormones, secretory capacity, and vulnerability to infection with HIV-1. Some studies have required the presence of inflammation detected by Gram staining of endocervical secretions to substantiate the clinical diagnosis of cervicitis, whereas others have not collected information on endocervical induced bleeding. These inconsistencies highlight the need for the use of consistent definitions of cervicitis in clinical research protocols and management guidelines. Methods A search of the English-language literature during the years 20002005 was performed using the Medline computerized database of the US National Library of Medicine, using the Medical Subject Headings (MeSH) terms cervicitis and mucopurulent cervicitis. Abstracts from major STD-related meetings during the same period were also searched using the same terms and were considered if they had not yet resulted in published data. Authors of the abstracts were contacted for more information if necessary. Key questions were generated by review of these resources and in consultation with experts in the fields of infectious diseases and gynecology. The search of the published literature yielded 114 articles and 5 abstracts that addressed data to help answer key questions. Results
Should the diagnostic criteria for cervicitis be modified?Cervicitis is defined clinically by the presence of either mucopurulent discharge or easily induced bleeding (friability) at the endocervical os; more subtle signs include edema of the cervical ectropion (edematous ectopy) and the presence of an elevated number of polymorphonuclear leukocytes, as detected by Gram staining of a smear of endocervical secretions under high-power magnification (!1000, oil immersion). Easily induced bleeding may actually be a more sensitive indicator of cervical chlamydial infection than the presence of purulent exudate. Among 6230 women attending an STD clinic, of whom 2.1% had gonorrhea and 6.9% had C. trachomatis infection as detected by culture, induced bleeding had a positive predictive value (PPV) equal to that of mucopus (!40%) in the women at highest risk (!19 years of age) [4]. Only 77 (2.9%) of 2648 women "25 years of age had either of these infections in the absence of either mucopus or induced bleeding. Of note, the predictive value of individual cervical findings suggestive of cervicitis may vary with patients' age and other STD-related risk factors [5].
Data on the usefulness of endocervical Gram staining are conflicting. In the study noted above, inflammation defined by Gram staining was the sole indicator of either infection in only 15% of women (sensitivity, 26%; PPV, 21%). A smaller study also found a limited independent value of Gram staining; indeed, more than half of the samples obtained were deemed inadequate because of the presence of vaginal contamination [6, p. 103]. The sensitivity of Gram staining for detection of N gonorrhoeae at the cervix is only 50% [7, 8]. The definition of a positive test result is also poorly standardized. Clinic practice guidelines recommend threshold level cutoffs varying from 10 to 30 polymorphonuclear leukocytes per highhttp://cid.oxfordjournals.org/content/44/Supplement_3/S102.full Page 2 of 15
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power field to diagnose cervicitis. As expected, sensitivity increases and specificity decreases as this threshold cutoff is decreased [9]. Furthermore, quality control for the performance of this test is difficult to maintain. For these reasons, the Centers for Disease Control and Prevention 1993 STD treatment guidelines stopped including results of Gram staining as presumptive evidence for empirical treatment of chlamydial infection [10]. However, despite its limited utility, the test continues to be used in many settings, particularly STD clinics, and is still recommended by some investigators [6]. Although inflammatory changes on Papanicolaou smear are associated with an increased likelihood of detection of several STDs [11, 12], including C. trachomatis infection, N. gonorrhoeae infection, trichomoniasis, and human papillomavirus infection, this test is neither specific nor practical enough to direct empirical therapy for these STDs [13,14,1516]. Recent research has evaluated the predictive value of leukorrhea (>10 leukocytes per high-power field on microscopic examination of vaginal fluid). Among 194 women, 61% (118) of whom were pregnant and who had a combined gonorrhea and chlamydia prevalence of 11% diagnosed by nucleic acid amplification testing (NAAT), the PPV of leukorrhea was 74% overall (20 of 27 women). The PPV was 92% (11 of 12) among nonpregnant women, versus 60% (9 of 15) among pregnant women [17]. The negative predictive value of leukorrhea was high (92%99%). Notably, induced bleeding was uncommon in this population (prevalence, 3.1%), and the prevalence of endocervical mucopus was not reported. Other data indicate that the absence of leukorrhea may be especially helpful in weighing against the presence of cervical STDs among women with bacterial vaginosis (BV) [18, 19]. Incorporating measurement of vaginal polymorphonuclear leukocytes in the evaluation of cervicitis may help to guide appropriate presumptive treatment of chlamydia and gonorrhea, but larger studies in diverse populations are needed.
What causes cervicitis, and how should this inform its diagnostic evaluation?C. trachomatis and N. gonorrhoeae remain important causes of cervicitis. Evidence continues to support NAATs as the preferred diagnostic assays for these STDs. NAATs have markedly enhanced sensitivity relative to earlier generations of diagnostic tests, while maintaining excellent specificity [20,21,2223], and they perform equally well in the presence of menses or mucopus [5]. Importantly, the sensitivity of NAATs performed on urine or vaginal swab specimens in detecting cervical chlamydia or gonorrhea is only slightly lower than that of NAATs performed directly on cervical swab specimens; therefore, either of these specimens can be used to assist in making a specific diagnosis of these STDs [24,25,2627]. These specimen types are particularly useful in settings where pelvic examinations cannot be performed.
Both Trichomonas vaginalis and genital herpes are associated with cervicitis. T. vaginalis can cause an erosive inflammation of the ectocervical epithelium, classically manifesting as strawberry cervix or
colpitis macularis. This process may cause a range of epithelial disruption, from small isolated petechiae to large punctuate hemorrhages with surrounding areas of pale mucosa. The pathogenesis of these lesions probably arises, in part, from the variety of cytotoxic factors that T. vaginalis elaborates, including cysteine proteases, which degrade cervicovaginal epithelial protective factors, most notably secretory leukocyte protease inhibitor [28]. Why only a subset of women develop evident cervical changes with trichomoniasis is not clear. Possible reasons include a direct relationship between quantitative burden of T. vaginalis, strain variation, or host factors that might increase susceptibility to cervical inflammation [29,3031]. A point-of-care antigen-based
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detection assay for T. vaginalis is now available (OSOM Trichomonas Rapid Test; Genzyme), with a sensitivity of 83.3% and specificity of 98.8% in a recent large study [32]. Genital infection with herpes simplex viruses (HSVs) causes cervicitis, most overtly in women with severe clinical manifestations of primary HSV-2 infection. Typically, cervicitis in this setting is characterized by diffuse erosive and hemorrhagic lesions, usually in the ectocervical epithelium, and is often accompanied by frank ulceration. Cervicitis is thought to occur in !15%20% of women with clinically evident primary HSV-2 genital infection [33]. In these cases, manifestations of primary HSV-2 genital infection are usually evident in the vulvar and/or introital epithelium. Cervicitis may accompany clinical recurrences of genital HSV-2 infection; however, it is typically less severe than that seen during primary infection. Subclinical shedding of HSV-2 does not appear to be directly related to cervicitis [34]. HSV-1 may also cause cervicitis; however, the manifestations are typically less severe and usually occur only during the primary genital infection [33]. A possible association between BV and cervicitis, independent of concomitant chlamydial and gonococcal infection, has emerged in several recent studies [35,36,3738]. Moreover, intravaginal antibiotic therapy for BV in the treatment regimen for women with cervicitis was associated with enhanced rates of resolution of cervicitis in 2 studies [39, 40]. Marrazzo et al. [38] reported that, among 424 women with BV, cervicitis was relatively common, occurring in 15%; in the overwhelming majority of women (87%), it was not associated with NAAT-based detection of cervical chlamydia or gonorrhea. In this study, increasing age, fewer years of formal education, report of a new male sex partner or of a current female sex partner, morerecent receptive oral sex, and absence of H2O2-producing Lactobacillus species were independently associated with an increased likelihood of cervicitis among women with BV. Intriguingly, vaginal colonization with H2O2-producing Lactobacillus species was associated with a 60% reduction in the likelihood of cervicitis. The mechanism by which BV might cause cervicitis is not clear, although it is probably multifactorial. Cervical shedding of HIV is increased in women with BV, suggesting that BV itself may have direct effects at the endocervical mucosa [41, 42]. Cytokines that help to regulate the normal function of mucosal defense systems include secretory leukocyte protease inhibitor, which helps to maintain healthy vaginal mucosa and levels of which are decreased in the presence of several STDs [28]; IL-10, which may increase the susceptibility of macrophages to HIV-1 infection [43]; and IL-1", which has been associated with a higher number of vaginal neutrophils in women with BV [44]. Even when vaginal flora is normal, the balance of pro- versus anti-inflammatory cervical cytokines may play a key role in modulating evident cervical inflammation and in permitting ascension of STD or other potential pathogens to the upper genital tract. One recent study demonstrated that a finding of decreased levels of cervical proinflammatory cytokinesIL-1", IL-6, and IL-8was associated with an increased likelihood of clinical chorioamnionitis [45]. The role of proinflammatory vaginal cytokines, such as IL-1", IL-6, and IL-8, is also supported by the observation that levels of these cytokines decrease after successful treatment of BV [46]. Finally, new bacteria that are highly specific for BV have recently been identified using molecular approaches [47, 48]; applying similar diagnostic techniques to cervical samples might elucidate a role for these organisms as cervical pathogens.
Mycoplasma genitalium has recently been implicated as a sexually transmissible cause of cervicitis [49, 50] and of acute endometritis [51]. Manhart et al. [49] studied archived endocervical fluid samples collected from 779 women attending an STD clinic during 19841986. Of the 719 samples that contained material that was PCR amplifiable, women with M.
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genitalium isolated were 3.3 times more likely to have cervicitis as defined by the presence of mucopurulent discharge, easily induced bleeding, and Gram staining showing "30 polymorphonuclear leukocytes per highpower field. Detection of M. genitalium was associated with each of these individual findings. This association persisted even when multiple cofactors were accounted for, including chlamydial and gonococcal coinfection, the proliferative phase of the menstrual cycle, and age. The authors concluded that M. genitalium infection was independently associated with cervicitis in this population, may cause cervical inflammation, and should be considered among potential etiologies of cervicitis [48]. More-recent studies appear to confirm this preliminary finding [50], and efforts to examine the response of this organism to standard antibiotics used to treat cervicitis are under way. One small study suggested that a tetracycline-based regimen might be inferior to an azithromycin-based one [52]. However, a current estimate of the population-based prevalence of M. genitalium infection among women with cervicitis has not been determined, and there are inadequate data to support routine diagnostic testing for this organism or changes in current empirical therapy recommendations. Furthermore, establishing a definitive role for M. genitalium in the causation of cervicitis and other inflammatory genital syndromes will require prospective studies that examine the response of associated clinical syndromes to appropriate antibiotics, concurrent infection of sex partners, and the true predilection of the anatomical site for this intriguing organism. Like Mycoplasma pneumoniae, M. genitalium appears to be sensitive to macrolides and tetracyclines, but further study is required to confirm the efficacy of these antibiotics in curing lower genital tract infection with this organism. M. genitalium is difficult to culture and, to date, clinical studies have depended on PCR for its detection. The implication of this fact for determining microbiological cure in such studies is not yet clear.
The role of other infectious agents in causing cervicitis is less clear. Cytomegalovirus, a herpesvirus that can be sexually transmitted, has been isolated in a small number of studies [53]. Cervical shedding of human T cell lymphotrophic virus 1 was found to be associated with the presence of cervicitis as defined by Gram staining or by visible endocervical secretions, in a cohort of commercial sex workers in Peru [54]. Whether human T-cell lymphotrophic virus 1 and cytomegalovirus contribute directly to cervical inflammation or are simply shed in higher concentrations during episodes of cervicitis is not known. Various case reports have attributed the presence of cervicitis in individual women to infection with certain Streptococcus species [55,5657]most notably, S. agalactiae (group B streptococcus) and S. pyogenes. However, reliable estimates of how commonly this might occur, if a causal relationship does indeed exist, are not available. The data are inadequate to inform a consistent diagnostic or therapeutic approach to these organisms in women with cervicitis. Substances that erode cervicovaginal mucosa or cause an irritant mucositis include chemical douches [58, 59], some spermicides (specifically, those with surfactant properties; nonoxynol-9 is the prototype), and chemical deodorants and should be considered among the potential causes of cervical inflammatory syndromes. Because at least 2 studies have demonstrated harm resulting from use of nonoxynol-9 [60, 61], and because none have shown clear benefit, this preparation cannot be recommended for the purpose of preventing STDs [62, 63]. In summary, the evaluation of cervicitis is complex because the process of endocervical inflammation may be mediated through several different pathways; moreover, the majority of cervical infections with STD-causing pathogens do not result in evident clinical syndromes, causing either no inflammation or inflammation detectable only by measure of surrogate
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inflammatory markers (figure 1). table 1 lists possible causes of cervicitis other than those resulting from infection with known pathogens. An endocervical local inflammatory process might be induced and maintained through the effects of as-yet-undiscovered pathogens, persistently abnormal vaginal flora, or a primary host autoimmune response. Such processes may be further modulated by the effect of endogenous and exogenous hormones. Fastidious or uncultivatable bacteria identified through the application of molecular detection methods, primarily application of broad-range 16S ribosomal DNA analysis, recently have been associated with BV and upper genital tract infection in women, as well as with urethritis in men [47, 48, 51, 67, 68]. Extension of these approaches to the study of cervicitis could be revealing.
Figure 1
Relationships between sexually transmitted infectious agents and cervicovaginal inflammation: 3 possibilities. STI, sexually transmitted infection.
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Table 1
Factors that may play a role in cervicitis for which typical

sexually transmitted pathogens are not detected.
When should cervicitis be presumptively treated, and what antimicrobials should be used?Recommendations for empiric therapy of cervicitis have focused primarily on C. trachomatis and N. gonorrhoeae. The 2002 Centers for Disease Control and Prevention STD treatment guidelines [69, p. 32] recommended that empirical treatment for these STDs in women with cervicitis should be considered for a patient who is suspected of having gonorrhea and/or chlamydia if a) the prevalences of these infections are high in the patient population and b) the patient might be difficult to locate for treatment. These recommendations did not incorporate a risk stratification to help target provision of presumptive therapy for chlamydia or gonorrhea in women with cervicitis. Moreover, potential alternative etiologies of cervicitis, such as genital herpes and trichomoniasis, were not addressed.
Young age consistently remains the most powerful predictor of both C.
trachomatis infection and N. gonorrhoeae infection. Because C. trachomatis infection is highly prevalent [70], data strongly support the use of presumptive therapy for this pathogen in women with cervicitis who are !25 years of age. The decision to provide empirical therapy for gonococcal infection is more complex and should be informed by several factors that also inform the approach to selective screening for this pathogen [71, 72]. These factors include the prevalence of gonorrhea in the local setting (for example, in the clinic or the local community, if these are known), recent history of STDs (especially chlamydial or gonococcal infection in the prior year), STD-related individual risk assessment (particularly reports of new or multiple sex partners in the prior 60 days or transactional sex), and the likelihood that the patient will be available for treatment should a diagnostic test result be positive. For example,
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adolescents with cervicitis in many inner-city areas of the United States are candidates for presumptive therapy for gonorrhea [70, 73]. Consensus establishment of a threshold prevalence of gonorrhea or chlamydia above which presumptive therapy should be provided would be extremely useful. Few data are available to fully advise clinicians on the decision to provide presumptive therapy for cervicitis among women >25 years of age. Some experts recommend at least 1 course of therapy for chlamydial infection in these women, whether or not specific risk factors are reported. Again, individual risk assessment and the likelihood that the patient will be available for treatment should a diagnostic test result be positive should inform the decision to treat. Recent history of STDs (especially chlamydial or gonococcal infection in the prior year) should also prompt consideration of presumptive therapy. Recurrent infection with C.
trachomatis is very common among women, ranging from 8% to 25% in several studies [74, 75], and probably relates predominantly to resumption of unprotected sex with untreated partners.
For all women with cervicitis, concomitant vaginal conditions, particularly BV and trichomoniasis, should be treated if present, and genital herpes should be considered. Data to help guide the need for treatment targeting
M. genitalium are not available, nor is optimum treatment for infection with this organism defined. table 2 lists specific therapeutic approaches to common pathogens that may cause cervicitis.
Table 2
Etiologies of cervicitis and suggested management.
How should nongonococcal, nonchlamydial cervicitis be managed?A vexing clinical problem is that, in many cases of cervicitis, neither C. trachomatis or N. gonorrhoeae is detected, even when highly sensitive diagnostic tests are used [1, 4, 79, 80]. For example, chlamydial or gonococcal infection was detected by culture in only 20% of 1028 women with either cervical mucopus or easily induced bleeding who attended a Seattle STD clinic during 19951999 [4]. More recently, among 133 women seeking care at STD clinics, 47.4% had no etiology, as assessed by NAAT for C. trachomatis, N. gonorrhoeae, M. genitalium, and T. vaginalis [81]. Nonetheless, cervicitis occurring in the absence of detectable gonococcal or chlamydial infection may confer an increased risk of poor pregnancy outcome [82] and predict upper genital tract disease [56, 83, 84]. Currently, the role of M. genitalium in these complications is unknown. Investigation of the natural history of cervicitis in which neither C. trachomatis or N. gonorrhoeae is detected is needed.
The limited available data suggest that antibiotics aimed at C. trachomatis and N. gonorrhoeae do not adequately treat nonchlamydial, nongonococcal cervicitis. Intriguingly, this contrasts with the parallel syndrome in mennonchlamydial, nongonococcal urethritisin which single-dose therapy with azithromycin is effective [85]. Although the combination of doxycycline and amoxicillin initially was effective in treating cervicitis among STD clinic clients in one study, high rates of persistent or recurrent cervicitis (23% and 33%, respectively) were observed 3 months after treatment, usually in the absence of detectable
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infection with C. trachomatis, N. gonorrhoeae, genital mycoplasma, or G. vaginalis (a surrogate measure of BV) [86]. In another study, treatment with ofloxacin yielded similar improvement in cervicitis, regardless of whether C. trachomatis was detected [87]. Finally, among 51 women with cervicitis and BV who were randomized to receive doxycycline and ofloxacin and either intravaginal metronidazole or placebo, those who received metronidazole had a higher rate of resolution of cervicitis at 2 and 4 weeks after treatment, and women whose BV resolved were more likely to have resolution of cervicitis at 2 weeks, regardless of what regimen they received [40]. Management of cervicitis for which neither identifiable STDs nor BV plays a role is empirical, and there are no data to recommend one approach over another. However, some physicians opt to provide a brief course of broad-spectrum therapy active against C. trachomatis, N. gonorrhoeae, and anaerobes [75].
How should persistent cervicitis be managed?Although providers commonly report the occurrence of persistent signs of cervical inflammation in women empirically treated for chlamydial and gonococcal cervicitis, there is no standard definition of persistent cervicitis, and there are no data to help clarify the epidemiology of this condition. The 2002 STD treatment guidelines [69, p. 32] stated that additional antimicrobial therapy may be of minimal benefit; however, no controlled clinical trials on this topic have been reported. Approaches include more extended courses of broad-spectrum antibiotics or ablative therapy, as described in a useful overview by Nyirjesy [79]. The value of repeated or prolonged administration of antibiotic therapy for this condition is unknown, but most experts feel it is unlikely to be of benefit. How should sex partners of women with cervicitis be managed?The 2002 STD treatment guidelines [69, p. 32] stated that sex partners should be managed as appropriate for the identified or suspected STDnamely, chlamydia, gonorrhea, or trichomoniasisin the index patient. This recommendation is consistent with partner management guidelines for women in whom these pathogens are actually detected. More problematic is the management of partners of women with cervicitis who are judged to be at high risk for chlamydial and/or gonococcal infection but have a low likelihood of returning to the clinic or of following up on the results of diagnostic testing. Arranging for evaluation of sex partners in these cases is challenging. In the absence of a specific STD diagnosis and of data to support efficacy of presumptive antibiotic therapy, clinicians may have difficulty communicating the nature and significance of the clinical syndrome and persuading women to discuss the diagnosis with sex partners. Moreover, results of STD and syndromic diagnostic evaluation (for example, for urethritis) may be negative in the partner even if an identifiable STD was the original culprit in the index patient [88]. In these cases, clinicians are required to make their best judgment as to their level of suspicion of infection in the index patient and to treat sex partners accordingly. More data in this area are clearly needed, particularly because program resources for partner management are limited. Should cervicitis be managed differently in HIV-infected women?Cure rates for the treatment of cervicitis caused by typical cervical and vaginal infections (chlamydia, gonorrhea, and trichomoniasis) do not appear to differ for HIV-infected women. However, emerging data strongly suggest that cervicitis (including nonchlamydial, nongonococcal cervicitis) increases the quantity of HIV shed at the endocervical canal [89] and that treatment of cervicitis is associated with a reduction in HIV load [90]. Thus, treatment of cervicitis might reduce a woman's risk of transmitting HIV to sex partners, and, therefore, a more aggressive approach to empirical treatment is indicated.
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Discussion Although our understanding of cervicitis and its pathogenesis has advanced considerably in the past 2 decades, many areas of uncertainty still remain. More research into the epidemiologic and clinical relationship between cervicitis and BV is needed, as is elucidation of the pathogenesis of this process if, in fact, there is a causal relationship. If the association between adequate levels of vaginal H2O2-producing lactobacilli and absence of cervicitis is confirmed, how do these organisms help to maintain a healthy cervicovaginal environment? The application of molecular approaches to detect pathogens that have eluded identification by traditional cultivation approaches could yield important new information about the cause of this syndrome. Because cervicitis increases the risk of poor pregnancy outcome, predicts upper genital tract disease, and is associated with increased shedding of HIV-1 from the cervix in the absence of chlamydial and gonococcal infection, determining the etiology of this condition should be a priority. Additionally, future research should focus on the cervical immune response to disruptions in the normal vaginal flora and to varying levels of sex hormones. The success of such studies will depend on the development of a consensus definition of cervicitis. Finally, appropriate presumptive management of cervicitis in women at relatively low risk for chlamydial or gonococcal infection, or in settings where gonococcal disease is relatively uncommon, is an important area for future study. acknowledgments
Supplement sponsorship.This article was published as part of a supplement entitled Sexually Transmitted Diseases Treatment Guidelines, sponsored by the Centers for Disease Control and Prevention. Potential conflicts of interest.J.M.M. is a consultant for K-V Pharmaceuticals and Mission Pharmacal and is on the speakers' bureaus of Merck and 3M Pharmaceuticals. D.H.M.: no conflicts.
2007 by the Infectious Diseases Society of America
References
1. Brunham RC, Paavonen J, Stevens CE, et al. Mucopurulent cervicitisthe ignored counterpart in women of urethritis in men. N Engl J Med 1984;311:1-6.
Medline Web of Science
2. Rees E, Tait A, Hobson D, Johnson FWA. Chlamydia in relation to cervical infection and pelvic inflammatory disease. In: Hobson D, Holmes KK, editors. Nongonococcal urethritis and related infections. Washington: American Society for Microbiology; 1977. p. 67.
Search Google Scholar
3. Centers for Disease Control Prevention, Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep 2006;55(RR-11):1-94.
Medline
4. Marrazzo JM, Handsfield HH, Whittington WL. Predicting chlamydial and gonococcal cervical infection: implications for management of cervicitis. Obstet Gynecol 2002;100:579-84.
CrossRef Medline Web of Science
5. Marrazzo JM, Johnson RE, Green TA, et al. Impact of patient characteristics on performance of nucleic acid amplification tests and DNA probe for detection of Chlamydia trachomatis in women with genital infections. J Clin Microbiol 2005;43:577-84.
Abstract/FREE Full Text
6. Myziuk L, Romanowski B, Brown M. Endocervical Gram stain smears and their usefulness in the diagnosis of Chlamydia trachomatis. Sex Transm Infect 2001;77:103-6.
Page 9 of 15
9/6/13 10:47 AM
7. Hook EW 3rd, Handsfield HH. Gonococcal infections in the adult. In: Holmes KK, Sparling PF, Mardh P-A, et al., editors. Sexually transmitted diseases. 3rd ed. New York: McGraw-Hill; 1999. p. 451-66.
8. Manavi K, Young H, Clutterbuck D. Sensitivity of microscopy for the rapid diagnosis of gonorrhoea in men and women and the role of gonorrhoea serovars. Int J STD AIDS 2003;14:390-4.
9. Manavi K, Conlan R, Barrie G. The performance of microscopic cervicitis for the detection of chlamydial infection. Sex Transm Infect 2004;80:415.
FREE Full Text
10. Centers for Disease Control Prevention. 1993 Sexually transmitted diseases treatment guidelines. MMWR Morb Mortal Wkly Rep 1993;42:1-102.
Medline
11. Kiviat NB, Paavonen JA, Wolner-Hanssen P, et al. Histopathology of endocervical infection caused by Chlamydia trachomatis, herpes simplex virus, Trichomonas vaginalis, and Neisseria gonorrhoeae. Hum Pathol 1990;21:831-7.
12. Kiviat NB, Wolner-Hanssen P, Eschenbach DA, et al. Endometrial histopathology in patients with culture-proved upper genital tract infection and laparoscopically diagnosed acute salpingitis. Am J Surg Pathol 1990;14:167-75.
13. Addiss DG, Vaughn ML, Golubjatnikov R, Pfister J, Kurtycz DF, Davis JP. Chlamydia trachomatis infection in women attending urban midwestern family planning and community health clinics: risk factors, selective screening, and evaluation of nonculture techniques. Sex Transm Dis 1990;17:138-46.
14. Bertolino JG, Rangel JE, Blake RL Jr, Silverstein D, Ingram E. Inflammation on the cervical Papanicolaou smear: the predictive value for infection in asymptomatic women. Fam Med 1992;24:447-52.
Medline
15. Edelman M, Fox A, Alderman E, et al. Cervical Papanicolaou smear abnormalities and Chlamydia trachomatis in sexually active adolescent females. J Pediatr Adolesc Gynecol 2000;13:65-9.
CrossRef Medline
16. Garozzo G, Lomeo E, La Greca M, et al. Chlamydia trachomatis diagnosis: a correlative study of pap smear and direct immunofluorescence. Clin Exp Obstet Gynecol 1993;20:259-63.
Medline
17. Hakakha MM, Davis J, Korst LM, Silverman NS. Leukorrhea and bacterial vaginosis as in-office predictors of cervical infection in high-risk women. Obstet Gynecol 2002;100:808-12.
18. Geisler WM, Yu S, Venglarik M, Schwebke JR. Vaginal leucocyte counts in women with bacterial vaginosis: relation to vaginal and cervical infections. Sex Transm Infect 2004;80:401-5.
19. Steinhandler L, Peipert JF, Heber W, Montagno A, Cruickshank C. Combination of bacterial vaginosis and leukorrhea as a predictor of cervical chlamydial or gonococcal infection. Obstet Gynecol 2002;99:603-7.
20. Koumans EH, Johnson RE, Knapp JS, St Louis ME. Laboratory testing for Neisseria gonorrhoeae by recently introduced nonculture tests: a performance review with clinical and public health considerations. Clin Infect Dis 1998;27:1171-80.
21. Black CM, Marrazzo J, Johnson RE, et al. Head-to-head multicenter comparison of DNA probe and nucleic acid amplification tests for Chlamydia trachomatis infection in women performed with an improved reference standard. J Clin Microbiol 2002;40:3757-63.
22. Cosentino LA, Landers DV, Hillier SL. Detection of Chlamydia trachomatis and Neisseria gonorrhoeae by strand displacement amplification and relevance of the amplification control for use with vaginal swab specimens. J Clin Microbiol 2003;41:3592-6.
Page 10 of 15
9/6/13 10:47 AM
23. Golden MR, Hughes JP, Cles LE, et al. Positive predictive value of Gen-Probe APTIMA Combo 2 testing for Neisseria gonorrhoeae in a population of women with low prevalence of N. gonorrhoeae infection. Clin Infect Dis 2004;39:1387-90.
24. Shafer MA, Moncada J, Boyer CB, Betsinger K, Flinn SD, Schachter J. Comparing first-void urine specimens, self-collected vaginal swabs, and endocervical specimens to detect Chlamydia trachomatis and Neisseria gonorrhoeae by a nucleic acid amplification test. J Clin Microbiol 2003;41:4395-9.
25. Schachter J, McCormack WM, Chernesky MA, et al. Vaginal swabs are appropriate specimens for diagnosis of genital tract infection with Chlamydia trachomatis. J Clin Microbiol 2003;41:3784-9.
26. Chernesky MA, Hook EW 3rd, Martin DH, et al. Women find it easy and prefer to collect their own vaginal swabs to diagnose Chlamydia trachomatis or Neisseria gonorrhoeae infections. Sex Transm Dis 2005;32:729-33.
27. Schachter J, Chernesky MA, Willis DE, et al. Vaginal swabs are the specimens of choice when screening for Chlamydia trachomatis and Neisseria gonorrhoeae: results from a multicenter evaluation of the APTIMA assays for both infections. Sex Transm Dis 2005;32:725-8.
28. Draper D, Landers D, Krohn M, Hillier S, Wiesenfeld H, Heine R. Levels of vaginal secretory leukocyte protease inhibitor are decreased in women with lower reproductive tract infections. Am J Obstet Gynecol 2000;183:1243-8.
29. Fiori PL, Rappelli P, Addis MF. The flagellated parasite Trichomonas vaginalis: new insights into cytopathogenicity mechanisms. Microbes Infect 1999;1:149-56.
30. Petrin D, Delgaty K, Bhatt R, Garber G. Clinical and microbiological aspects of Trichomonas vaginalis. Clin Microbiol Rev 1998;11:300-17.
31. Schwebke JR. Update of trichomoniasis. Sex Transm Infect 2002;78:378-9.

32. Huppert JS, Batteiger BE, Braslins P, et al. Use of an immunochromatographic assay for rapid detection of Trichomonas vaginalis in vaginal specimens. J Clin Microbiol 2005;43:684-7.
33. Corey L, Wald A. Genital herpes. In: Holmes KKSP, Mardh P-A, Lemon SM, Stamm WE, Piot P, Wasserheit J, editors. Sexually transmitted diseases. 3rd ed. New York: McGraw-Hill; 1999. p. 285-312.
34. Koelle DM, Benedetti J, Langenberg A, Corey L. Asymptomatic reactivation of herpes simplex virus in women after the first episode of genital herpes. Ann Intern Med 1992;116:433-7.
35. Keshavarz H, Duffy SW, Sadeghi-Hassanabadi A, Zolghadr Z, Oboodi B. Risk factors for and relationship between bacterial vaginosis and cervicitis in a high risk population for cervicitis in Southern Iran. Eur J Epidemiol 2001;17:89-95.
36. Peipert JF, Montagno AB, Cooper AS, Sung CJ. Bacterial vaginosis as a risk factor for upper genital tract infection. Am J Obstet Gynecol 1997;177:1184-7.
37. Willmott FE. Mucopurulent cervicitis: a clinical entity? Genitourin Med 1988;64:169-71.
38. Marrazzo JM, Wiesenfeld HC, Murray P, et al. Risk factors for mucopurulent cervicitis among women with bacterial vaginosis. J Infect Dis 2006;193:617-24.
39. Schwebke JR, Schulien MB, Zajackowski M. Pilot study to evaluate the appropriate management of patients with coexistent bacterial vaginosis and cervicitis. Infect Dis Obstet Gynecol 1995;3:119-22.
CrossRef Medline
Page 11 of 15
9/6/13 10:47 AM
40. Schwebke JR, Weiss HL. Interrelationships of bacterial vaginosis and cervical inflammation. Sex Transm Dis 2002;29:59-64.
41. Cu-Uvin S, Hogan JW, Caliendo AM, Harwell J, Mayer KH, Carpenter CC. Association between bacterial vaginosis and expression of human immunodeficiency virus type 1 RNA in the female genital tract. Clin Infect Dis 2001;33:894-6.
42. Seck K, Samb N, Tempesta S, et al. Prevalence and risk factors of cervicovaginal HIV shedding among HIV-1 and HIV-2 infected women in Dakar, Senegal. Sex Transm Infect 2001;77:190-3.
43. Cohen CR, Plummer FA, Mugo N, et al. Increased interleukin-10 in the endocervical secretions of women with non-ulcerative sexually transmitted diseases: a mechanism for enhanced HIV-1 transmission? AIDS 1999;13:327-32.
44. Cauci S, Guaschino S, De Aloysio D, et al. Interrelationships of interleukin-8 with interleukin-1" and neutrophils in vaginal fluid of healthy and bacterial vaginosis positive women. Mol Hum Reprod 2003;9:53-8.
45. Simhan HN, Caritis SN, Krohn MA, Martinez de Tejada B, Landers DV, Hillier SL. Decreased cervical proinflammatory cytokines permit subsequent upper genital tract infection during pregnancy. Am J Obstet Gynecol 2003;189:560-7.
46. Yudin MH, Landers DV, Meyn L, Hillier SL. Clinical and cervical cytokine response to treatment with oral or vaginal metronidazole for bacterial vaginosis during pregnancy: a randomized trial. Obstet Gynecol 2003;102:527-34.
47. Ferris MJ, Masztal A, Aldridge KE, Fortenberry JD, Fidel PL Jr, Martin DH. Association of Atopobium vaginae, a recently described metronidazole resistant anaerobe, with bacterial vaginosis. BMC Infect Dis 2004;4:5.
CrossRef Medline
48. Fredricks DN, Fiedler TL, Marrazzo JM. Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med 2005;353:1899-911.
49. Manhart LE, Critchlow CW, Holmes KK, et al. Mucopurulent cervicitis and Mycoplasma genitalium. J Infect Dis 2003;187:650-7.
50. Schlicht MJ, Lovrich SD, Sartin JS, Karpinsky P, Callister SM, Agger WA. High prevalence of genital mycoplasmas among sexually active young adults with urethritis or cervicitis symptoms in La Crosse, Wisconsin. J Clin Microbiol 2004;42:4636-40.
51. Cohen CR, Manhart LE, Bukusi EA, et al. Association between Mycoplasma genitalium and acute endometritis. Lancet 2002;359:765-6.
52. Falk L, Fredlund H, Jensen JS. Tetracycline treatment does not eradicate Mycoplasma genitalium. Sex Transm Infect 2003;79:318-9.
53. McGalie CE, McBride HA, McCluggage WG. Cytomegalovirus infection of the cervix: morphological observations in five cases of a possibly under-recognised condition. J Clin Pathol 2004;57:691-4.
54. Zunt JR, Dezzutti CS, Montano SM, et al. Cervical shedding of human T cell lymphotropic virus type I is associated with cervicitis. J Infect Dis 2002;186:1669-72.
55. Buttigieg G. Cervicitis and urethritis caused by group B streptococcus: case report. Genitourin Med 1985;61:343-4.
56. Paavonen J, Kiviat N, Brunham RC, et al. Prevalence and manifestations of endometritis among women with cervicitis. Am J Obstet Gynecol 1985;152:280-6.
Page 12 of 15
9/6/13 10:47 AM
57. Paraskevaides EC, Wilson MC. Fatal disseminated intravascular coagulation secondary to streptococcal cervicitis. Eur J Obstet Gynecol Reprod Biol 1988;29:39-40.
58. Critchlow CW, Wolner-Hanssen P, Eschenbach DA, et al. Determinants of cervical ectopia and of cervicitis: age, oral contraception, specific cervical infection, smoking, and douching. Am J Obstet Gynecol 1995;173:534-43.
59. Scholes D, Stergachis A, Ichikawa LE, Heidrich FE, Holmes KK, Stamm WE. Vaginal douching as a risk factor for cervical Chlamydia trachomatis infection. Obstet Gynecol 1998;91:993-7.
60. Kreiss J, Ngugi E, Holmes K, et al. Efficacy of nonoxynol 9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes. JAMA 1992;268:477-82.
61. Richardson BA, Lavreys L, Martin HL. Evaluation of a low-dose nonoxynol-9 gel for the prevention of sexually transmitted diseases. Sex Transm Dis 2001;28:394-400.
62. Richardson BA. Nonoxynol-9 as a vaginal microbicide for prevention of sexually transmitted infections: it's time to move on. JAMA 2002;287:1171-2.
FREE Full Text
63. Wilkinson D, Tholandi M, Ramjee G, Rutherford GW. Nonoxynol-9 spermicide for prevention of vaginally acquired HIV and other sexually transmitted infections: systematic review and meta-analysis of randomised controlled trials including more than 5000 women. Lancet Infect Dis 2002;2:613-7.
64. Olmsted SS, Meyn LA, Rohan LC, Hillier SL. Glycosidase and proteinase activity of anaerobic gram-negative bacteria isolated from women with bacterial vaginosis. Sex Transm Dis 2003;30:257-61.
65. Brabin L. Interactions of the female hormonal environment, susceptibility to viral infections, and disease progression. AIDS Patient Care STDS 2002;16:211-21.
66. Sobel J. Current concepts: vaginitis. N Engl J Med 1997;337:1896-903.

67. Hebb JK, Cohen CR, Astete SG, Bukusi EA, Totten PA. Detection of novel organisms associated with salpingitis, by use of 16S rDNA polymerase chain reaction. J Infect Dis 2004;190:2109-20.
68. Mena L, Wang X, Mroczkowski TF, Martin DH. Mycoplasma genitalium infections in asymptomatic men and men with urethritis attending a sexually transmitted diseases clinic in New Orleans. Clin Infect Dis 2002;35:1167-73.
69. Centers for Disease Control Prevention. Sexually transmitted diseases treatment guidelines 2002. MMWR Recomm Rep 2002;51(RR-6):1-78.
Medline
70. Centers for Disease Control and Prevention. Sexually transmitted disease surveillance, 2004. Atlanta: Centers for Disease Control and Prevention; 2005. 71. Screening for gonorrhea: recommendation statement. Ann Fam Med 2005;3:263-7.
FREE Full Text
72. Mertz KJ, Levine WC, Mosure DJ, Berman SM, Dorian KJ, Hadgu A. Screening women for gonorrhea: demographic screening criteria for general clinical use. Am J Public Health 1997;87:1535-8.
73. Miller WC, Ford CA, Morris M, et al. Prevalence of chlamydial and gonococcal infections among young adults in the United States. JAMA 2004;291:2229-36.
74. Burstein GR, Zenilman JM, Gaydos CA, et al. Predictors of repeat Chlamydia trachomatis infections diagnosed by DNA amplification testing among inner city
Page 13 of 15
9/6/13 10:47 AM
females. Sex Transm Infect 2001;77:26-32.

75. Whittington WL, Kent C, Kissinger P, et al. Determinants of persistent and recurrent Chlamydia trachomatis infection in young women: results of a multicenter cohort study. Sex Transm Dis 2001;28:117-23.
76. Berman SM, Moran JS, Wang SA, Workowski KA. Fluoroquinolones, gonorrhea, and the CDC STD treatment guidelines. Sex Transm Dis 2003;30:528-9. author reply, 530.
77. Increases in fluoroquinolone-resistant Neisseria gonorrhoeae among men who have sex with menUnited States 2003 and revised recommendations for gonorrhea treatment 2004. Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep 2004;53:335-8.
Medline
78. Newman LM, Moran JS, Workowski KA. Update on the management of gonorrhea in adults in the United States. Clin Infect Dis 2007;44(Suppl 3):84-101. (in this supplement).
CrossRef
79. Nyirjesy P. Nongonococcal and nonchlamydial cervicitis. Curr Infect Dis Rep 2001;3:540-5.
CrossRef Medline
80. Paavonen J, Critchlow CW, DeRouen T, et al. Etiology of cervical inflammation. Am J Obstet Gynecol 1986;154:556-64.
81. Gaydos CA, Hardick A, Hardick J, Barnes M, Wood BJ. Program and abstracts of the American Society for Microbiology 106th General Meeting (Orlando, FL). Washington, DC: American Society for Microbiology; 2006. Use of Gen-Probe APTIMA tests to detect multiple etiologies of urethritis and cervicitis in sexually transmitted disease clinics [abstract C-086]; p. 63.
82. Nugent RP, Hillier SL. Mucopurulent cervicitis as a predictor of chlamydial infection and adverse pregnancy outcome. The Investigators of the Johns Hopkins Study of Cervicitis and Adverse Pregnancy Outcome. Sex Transm Dis 1992;19:198-202.
83. Peipert JF, Ness RB, Soper DE, Bass D. Association of lower genital tract inflammation with objective evidence of endometritis. Infect Dis Obstet Gynecol 2000;8:83-7.
CrossRef Medline
84. Wiesenfeld HC, Hillier SL, Krohn MA, et al. Lower genital tract infection and endometritis: insight into subclinical pelvic inflammatory disease. Obstet Gynecol 2002;100:456-63.
85. Stamm WE, Hicks CB, Martin DH, et al. Azithromycin for empirical treatment of the nongonococcal urethritis syndrome in men: a randomized double-blind study. JAMA 1995;274:545-9.
86. Paavonen J, Roberts PL, Stevens CE, et al. Randomized treatment of mucopurulent cervicitis with doxycycline or amoxicillin. Am J Obstet Gynecol 1989;161:128-35.
87. Chandeying V, Sutthijumroon S, Tungphaisal S. Evaluation of ofloxacin in the treatment of mucopurulent cervicitis: a response of chlamydia-positive and chlamydia-negative forms. J Med Assoc Thai 1989;72:331-7.
Medline
88. Stekler J, Bachmann L, Brotman RM, et al. Concurrent sexually transmitted infections (STIs) in sex partners of patients with selected STIs: implications for patient-delivered partner therapy. Clin Infect Dis 2005;40:787-93.
89. Wright TC Jr, Subbarao S, Ellerbrock TV, et al. Human immunodeficiency virus 1 expression in the female genital tract in association with cervical inflammation and ulceration. Am J Obstet Gynecol 2001;184:279-85.
90. McClelland RS, Wang CC, Mandaliya K, et al. Treatment of cervicitis is associated with decreased cervical shedding of HIV-1. AIDS 2001;15:105-10.
Page 14 of 15
9/6/13 10:47 AM
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