VaginitisKervicitis: Diagnosis and Treatment Options in a Limited Resource Environment Daniel
V. Landers,
MD
Associate Professor and Director Division of Reproductive Infectious Diseases and Immunology Department of Obstetrics, Gynecology and Reproductive Sciences University of Pittsburgh, School of Medicine and Magee Womens Hospital Associate Scientist, Magee Womens Research Institute Pittsburgh, Pennsylvania
V
aginal and cervical infections, particularly by sexually transmitted organisms, are a common and important health-related problem to military women. These infections not only affect the mental w and physical health of women, they may adversely affect the ability of military women to perform their duties. These infections frequently produce symptoms sufficient to cause pain, irritation, foul odor, discharge, intense itching, and even sleep loss. These conditions and symptoms may also cause embarrassment to women working and living in close quarters, and also lead to decreased productivity and time off from the workplace for evaluation, diagnosis, and treatment. All of these factors may significantly impact the ability and readiness of military women to perform their assigned tasks and duties. Furthermore, the adequately trained health care providers, laboratories, and advanced technology required for rapid diagnosis and treatment of these conditions may not always be readily available to deployed military women especially while in remote areas or developing countries. Speculum examination requiring special tables, stirrups, directed lighting, and other specialty equipment may not be easily accessible in many deployment situations.
SCOPE OF THE PROBLEM Vaginitis and cervicitis occur in upward of 12 million women each year in the United States.r,’ These infections occur most commonly in the 2nd, 3rd and 4th decade of life. The prevalence of these infections is highest in the 17-25-yearold age group, particularly the sexually transmitted diseases (STDs). Thus, these infections will commonly occur among women in the U.S. Armed Services by virtue of their age range alone. Additional considerations including socioeconomic background, increased frequency of sexual activity, numbers of partners, and prevalence of STDs in their partner pool will enhance the risk of military women over the civilian population at large. For example, military 342
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The views, opinions, and/or findings reported in this article are those of the author(s) and should not be construed as official Department of Defense or other U.S. government agency positions, policies, or decisions. Published by Elsevier Science Inc. 1049-3867/96/$15.00 PII: S1049-3867(96)00061-8
women are more likely to meet and choose other military personnel as their sexual partners and there are sufficient data to indicate that deployed military men frequently engage in high-risk sexual behavior and contract STDs. In one study, of 1,744 military men deployed aboard ship for 6 months to South America, West Africa, and the Mediterranean, 49% reported prior sexual contact with a commercial sex worker and 22% reported a history of an STD before deployment. During the subsequent 6-month deployment, 42% reported sexual contact with a commercial sex worker, 10% acquired a new STD, and 10% reported inconsistent condom use. Recent preliminary reports from a survey of Army personnel indicate that 18% of women respondents report having had at least one STD over a 2-year period and this may be an underestimate, especially if women with an STD history were less likely to respond to the survey.4 In another study of 476 asymptomatic active duty army women presenting for routine pap smears, 39 (8.2%) tested positive for chlamydia;5 this is a high rate of asymptomatic chlamydia infection. These statistics are further compounded by the fact that only about 50% of all unmarried military personnel reported using a condom during their last intercourse and women under the age of 25 (the age group at highest risk for acquiring an STD) account for two-thirds of the enlisted women that are pregnant at any given time. There is additional accumulating evidence that other, less obvious factors may influence the high rate of STDs among military women. Statistics show that 31% of women on active duty in the U.S. Army smoke cigarettes of which 17% are heavy smokers. This is significantly higher than the number of smokers in the general population4 Several recent studies have demonstrated that smoking is a significant risk factor in the acquisition of numerous STDs including Chlamydia frachomatis, Neisseria gonorrhoeae, and pelvic inflammatory disease and its sequelae.6-8 Delayed diagnosis and treatment of STDs and urinary tract infections may very well lead to significant, even life-threatening, long-term sequelae. Serious upper genital tract infections, permanent infertility, and life-threatening ectopic pregnancies are all recognized and well-documented sequelae of lower urogenital tract infections in w0men.i” Recent studies also indicate that the presence of these cervical/vaginal STDs significantly increases the risk of human immunodeficiency virus (HIV) acquisition.9110
CHARACTERISTICS
OF THE INFECTIONS
The most common symptom of both vaginitis and cervicitis is an abnormal vaginal discharge. The patient is unable to discern cervical from vaginal infection. The sexually transmitted organisms N. gonorrhoeae and C. frachomatis are responsible for most cases of cervicitis while Trichomonas vaginalis, Candida species, and bacterial vaginosis account for nearly all cases of infectious vaginitis/vaginosis.2-4,11,12 Chlamydial infections are the most common bacterial STDs in the developed world. There are an estimated 4 million chlamydial infections annually in the United States alone with over 2 million occurring in women.2,13z14Over one million cases of gonorrhea occur in the United States each year.2 Presenting complaints include vaginal discharge, dysuria, and abnormal uterine bleeding. Both gonorrhea and chlamydia can and often do present with minimal or very subtle symptoms necessitating screening and/or testing for minimal symptomatology in the “at risk’ populations. Sequelae of these infections include pelvic inflammatory disease, ectopic pregnancy, permanent infertility, and chronic, often debilitating pelvic pain2,i4
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Infectious vaginitis and vaginosis account for some B-10 million outpatient visits a year in the United States.‘” The three conditions accounting for the vast majority of these cases are trichomonas vaginitis, candida vaginitis, and bacterial vaginosis. Vaginal yeast infections commonly occur in women. It has been estimated that 75% of women will have at least one episode of yeast vulvovaginitis, with 4045% having 2 or more episodes.16 The predominant organism causing these infections is Candida albicans, and occasionally nonalbicans candidal species (Candida tropicalis, Candida [7’aruIopsisl glabrata or other Candida species). The most common presenting complaint is vaginal and/or vulvar pruritis with or without vaginal discharge; however some 30% of women with yeast infections may present with discharge alone. An estimated 3 million cases of trichomoniasis occur in the United States annually. This infectious form of vaginitis is caused by T. vaginalis, a sexually transmitted motile protozoan. It accounts for approximately lo-15% of all cases of clinically evident vaginal infections. Infection with this organism is most often characterized by a copious, foul-smelling discharge but the clinical presentation can be quite variable including a significant number of women without specific vaginal complaints. Bacterial vaginosis (formerly known as Gardnerella vaginitis, Haemophilis vaginitis, or nonspecific vaginitis) is the most common cause of malodorous vaginal discharge in women.” It has been estimated to be the etiology in as many as 45% of women with vaginitis/vaginosis.‘8 Bacterial vaginosis (BV) is caused by a shift in the vaginal flora from the normal high concentrations of hydrogen peroxide-producing lactobacilli to a mixed flora consisting of a high concentration of anaerobic organisms, Gardnerella vaginalis, and Mycoplasma hominis.” This shift in flora is associated with a homogenous, white vaginal discharge, elevated pH (>4.5), the production of amines, and the presence of clue cells.
GOLD STANDARD CERVICAL/VAGINAL
DIAGNOSIS OF INFECTIONS
The clinical presentation of cervical/vaginal infections in women is highly variable ranging from asymptomatic to debilitating symptoms from deepseated infection. The more common presentations include symptoms such as persistent and often foul-smelling vaginal discharge, intense vulvovaginal pruritis and irritation, dysuria, and/or pelvic pain. Diagnostic accuracy based on clinical symptoms alone varies dramatically and is quite subjective. Clinical suspicions are confirmed with specific laboratory or office-based microscopic tests. The laboratory test with the greatest sensitivity and specificity will be considered the “gold standard.” While there is no official listing of the “gold standard” laboratory tests for a given organism or condition, there are a number of tests which are considered to have the highest sensitivity and specificity (shown in Table 1). Table 1. GOLD STANDARD Infection
Cervicitis/urethritis
Chlamydia trachomatis
Bacterial vaginosis Candida vaginitis Trichomoniasis
Neisseria gonorrhoeae Multiple Candida Trichomonas vaginalis
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Polymerase chain reaction, culture Culture Gram stain Culture Culture
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These confirmatory tests are often expensive and take from a few days to as much as a week before a definitive result is available. It is crucial that rapid, relatively inexpensive, and reasonably accurate diagnostic tests be developed. They would have to be reliable, sensitive, and specific to minimize overtreatment as well as undertreatment.
RAPID TESTS Each of the cervical/vaginal infections in women have some characteristicseither clinical, microbiological, or immunological, which may be exploited in the development of simple, rapid diagnostic testing. Chlamydia, gonorrhea, and trichomoniasis all induce the migration of inflammatory cells when they infect the lower female genital tract. Lactoferrin is a stable iron-binding glycoprotein found concentrated in secondary granules in inflammatory cells but not found in lymphocytes or monocytes.20,21 This represents an ideal marker for inflammatory cells which have migrated to the lower genital tract in response to these infections. Preliminary investigations correlating genital tract lactoferrin levels with chlamydia, gonorrhea, and trichomoniasis have been reported in abstract form but have yet to appear in the literature. Two consistent characteristics of women with bacterial vaginosis are the high vaginal pH and the presence of amines.19Y22The vaginal pH is raised as the glucose fermenting lactobacilli (which produce lactic acid) are replaced with a mixed flora whose metabolic byproducts are less acidic. The vaginal pH is the most sensitive of the tests for bacterial vaginosis but it lacks a high degree of specificity. The amine odor test is based on the release of amines (putrecine, cadaverine, trimethylamine) following alkalinization with 10% potassium hydroxide. The sensitivity of this test has been reported to be as high as 87% with 98% specificity.23 The currently used diagnostic tests also require a speculum examination. This requires an experienced clinician as well as specialized equipment including a pelvic exam table with stirrups. We have recently completed several studies utilizing self-collected vaginal specimens to diagnose chlamydial, gonococcal, and trichomonal infections. In the first of these studies vaginal (introital) swabs were collected from 300 women by the clinician.‘* In 200 of these women a self-collected introital sample and a urine sample were also submitted for chlamydial polymerase chain reaction @‘CR) testing. Women were instructed on proper introitus specimen collection by the study personnel, with a pictogram provided as additional reference. Self-collection was performed in strict privacy. The patient placed a dacron-tipped swab 1 inch into the distal vagina for 10 seconds. The swabs were then placed by the patient into PCR transport media. Women then underwent pelvic examination, and cervical, urethral, and vaginal specimens were obtained for chlamydia PCR, culture, and enzyme immunoassay (EIA). Women were considered to be infected with chlamydia if any site was positive by culture or in addition, they were positive by PCR and negative by culture with confirmation by PCR with a second primer. Overall, 37 (12.3%) of the women were infected with C. trachomatis. The sensitivity of PCR on introital samples was 92% and the specificity was 100%. This technique performed as well as any other method of collection and testing including: endocervical PCR, endocervical culture, endocervical EIA, urethral PCR, and urethral culture. Among the 200 women who self-collected vaginal introital samples, again the sensitivity and specificity was as good or better than samples collected from any other site. The self-collected samples had a lower sensitivity (81 vs 92%) compared to clinician-obtained samples. We have improved our patient instruction materials to increase self-collection sensitivity to optimize diagnostic accuracy.
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In subsequent studies we have evaluated this sampling site for the diagnosis of gonorrhea and trichomoniasis. In a study of 100 women undergoing vaginal introitus sampling for N. ganorrhoeae and tested by PCR, we found a sensitivity of 1OO%.25This was equivalent to endocervical culture and better than endocervical or urethral PCR (82% and 64% sensitivity, respectively). In our evaluation, 100 women were tested for T. vaginalis by PCR; all 15 women positive for this organism by culture and/or wet mount were identified by PCR of samples obtained by swabs from the vaginal introitus. These data strongly support our contention that vaginal introitus samples can be used to accurately diagnose chlamydial, gonococcal, and trichomonal infections in the lower female genital tract. Furthermore, the self-collection of vaginal introital samples was successful (no patients were unable to collect the samples), well accepted by the women, and may well enhance their willingness to undergo testing by imparting an element of privacy to specimen collection. The vaginal introitus sampling site provides easy access to vaginal secretions containing exfoliated cells from the lower genital tract, soluble cell products, and frequently organisms as well. Obtaining these samples is no more difficult than inserting a tampon, and can easily be accomplished by most women in a minute or less during a visit to a restroom. Therefore, self-collection is a feasible strategy for military women especially in a setting with suboptimal conditions.
TREATMENT
OPTIONS
A single dose of azithromycin, an azalide antibiotic, is as effective as doxycycline for 1 week as a treatment for chlamydial infection.27 It has further been shown to have good efficacy in eradicating lower genital tract gonorrhea when used in a 2 g dose. However, at this higher dose, significant gastrointestinal symptoms were reported in 35% of patients.” Studies of the efficacy of the lower 1 g dose in eradicating Neisseriu gonorrhoeue have been variable. In one study 25 of 27 (93%) of patients were cured with a single 1 g doseez9 In another study 76 of 82 (93%) of males were cured with gonococcal urethritis.30 Other smaller studies have suggested lower efficacy. Further studies are underway to determine if a 1 g dose will be sufficient to adequately treat uncomplicated gonorrhea. At present, additional coverage is necessary for effective eradication of gonorrhea. The vast majority of yeast infections (80-90%) respond to standard, single or multiple dose antifungal agents. Oral fluconazole in a single 150 mg dose has been shown to be an effective treatment for vaginal candidiasis with low toxicity and minimal side effects. In a review of 14 comparative and 14 noncomparative clinical studies conducted in 19 different countries a total of 3,929 patients were treated with fluconazole.31 A clinical response was demonstrated in 94% of the patients with a mycological cure in 85%. The drug was well tolerated and no serious adverse effects were reported in any of these trials. Metronidazole has long been the treatment of choice for trichomoniasis, most often administered in a 2 g single dose with cure rates between 86% and 97%.32 It has also been highly effective in the treatment of bacterial vaginosis with cure rates reported between 84% and 95%, depending on whether treatment was with a 2 g dose (84%) or a 7-day regimen.
CONCLUSIONS Technology and data now exist to diagnose cervical and vaginal infections in women with a fairly high degree of accuracy, but most of this technology is not available in a form that is currently useful in a limited resource environment. 346
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However, it is feasible develop simple, rapid,
using currently available and evolving technology to and sensitive self-tests for the most common treatable
cervical and vaginal infections in women. This would utilize self-sampling techniques and currently available dipstick tests combined with other tests in development (eg, rapid lactoferrin determinations). Single agent treatment regimens could be assigned according to test results. Considerable research to provide a usable test kit and to determine its diagnostic accuracy needs to be done.
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