The accuracy and efficacy of screening tests for Chlamydia trachomatis: a systematic review.

Screening women for lower genital tract infection with Chlamydia trachomatis is important in the prevention of pelvic inflammatory disease, ectopic pregnancy and infertility. This systematic review aims to state clearly which of the available diagnostic tests for the detection of C. trachomatis would be most effective in terms of clinical effectiveness. The review included all studies published from 1990 onward that evaluated diagnostic tests in asymptomatic, young, sexually active populations. Medline and Embase were searched electronically and key journals were hand-searched. Further studies were identified through the Internet and contact with experts in the field. All studies were reviewed by two reviewers and were scored by Irwig's assessment criteria. Additional quality assessment criteria included a documented sexual history and recording of previous chlamydial infection. The reviews were subjected to meta-analysis and meta-regression. The 30 studies that were included examined three types of DNA-based test--ligase chain reaction (LCR), PCR and gene probe--as well as enzyme immuno-assay (EIA). The results showed that while specificities were high, sensitivities varied widely across the tests and were also dependent on the specimen tested. Pooled sensitivities for LCR, PCR, gene probe and EIA on urine were 96.5%, 85.6%, 92% and 38%, respectively, while on cervical swabs the corresponding sensitivities of PCR, gene probe and EIA were 88.6%, 84% and 65%. Meta-analysis demonstrated that DNA amplification techniques performed best for both urine and swabs in low prevalence populations. We conclude that nucleic acid amplification tests used on non-invasive samples such as urine are more effective at detecting asymptomatic chlamydial infection than conventional tests, but there are few data to relate a positive result with clinical outcome.

Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species.

Ibuprofen, a non-steroidal anti-inflammatory drug, exhibited antimicrobial activity against Candida albicans and non-albicans strains. At 10 mg/ml, ibuprofen showed a rapid cidal activity against exponential growth phase C. albicans, accompanied by rapid and extensive leakage of intracellular K+, permeation to propidium iodide, lysis of spheroplasts and severe membrane ultrastructural alterations. These results indicate that the killing of Candida cells is due to direct damage to the cytoplasmic membrane. At 5 mg/ml, ibuprofen inhibited growth; however, it did not kill the yeasts and did not directly affect the cytoplasmic membrane. Evaluation of yeast metabolic vitality with the fluorescent probe FUN-1 showed that growth inhibition induced by the fungistatic drug concentration was due to metabolic alterations. The combination of ibuprofen with fluconazole resulted in synergic activity with eight of the 12 Candida strains studied, including four of the five fluconazole-resistant strains. The MICs of fluconazole for the fluconazole-resistant strains decreased 2-128-fold when the drug was associated with ibuprofen. When in combination with fluconazole, MICs for ibuprofen decreased by up to 64-fold for all the 12 strains studied. These results point to the practicability of using ibuprofen, alone or in combination with azoles, in the treatment of candidosis, particularly when applied topically, taking advantage of the drug's antifungal and anti-inflammatory properties.

Is the prevention of genital chlamydial infections by community involvement possible?

This chapter presents different means by which community initiatives have been undertaken to reduce the prevalence and incidence of genital and allied infections caused by Chlamydia trachomatis. As most of these infections in the majority of infected individuals do not produce symptoms that are likely to urge them to attend any health care unit, screening programmes are mandatory to be able to influence the epidemic of infections with this agent. In many societies there has been a skewed gender distribution in the number of chlamydia-positive persons; this probably indicates that diagnostic service activities have been directed more against one gender than the other. The important role of partner notification, as in the case of other sexually transmitted infections, has been documented. Different means of community initiative have included counselling of school children and groups of persons more likely to be infected. Counselling by the pharmacy has an important role in many societies. Selected cohorts have been offered - via the mass media, Internet, radio and television programmes - sampling kits which can be mailed to a laboratory for testing. The establishment of youth clinics has been found effective for detecting teenagers harbouring C. trachomatis, similarly to screening at antenatal clinics. The offer of free consultations, aetiological tests and therapy has been a part of community initiatives, mimicking the services offered for some of the classic sexually transmitted infections. This chapter considers the usefulness of different test methods and stresses the need to retest those found to be positive. Barriers to the successful introduction of screening activities and diagnostic services are also considered.

Influence of infection with Chlamydia trachomatis on pregnancy outcome, infant health and life-long sequelae in infected offspring.

This chapter deals with genital chlamydial infections in pregnancy and postpartum. There is increasing evidence that Chlamydia trachomatis infection may result in a number of adverse pregnancy outcomes, including early and late abortion, intrauterine infections of the fetus, stillbirth, prematurity, premature rupture of the membranes (PROM) and postpartum endometritis. Ectopic pregnancy is commonly associated with a previous tubal chlamydial infection where immunological reactions seem to play a role. C. trachomatis infection may be acquired as an intrauterine infection, as well as during transit through the birth channel, and this may result in neonatal conjunctivitis and/or pneumonia. The role of chlamydial infection in the sudden death syndrome has also been considered, but evidence so far is minimal. Neonatal chlamydial infection may cause life-long sequelae, such as obstructive lung disease. Genital chlamydial infections have been associated with problems in insemination and attempts at in vitro fertilization. The chapter also deals with screening of pregnant women for C. trachomatis and the treatment of infected mothers and their offspring.

Is there a need for rescreening of patients treated for genital chlamydial infections?

The present communication reviews reasons to perform rescreening of chlamydia-infected persons. It brings up difficulties to differentiate between relapse and reinfection. Studies on follow-up of chlamydia-positive cases after therapy are reviewed. It also highlights reasons for therapeutic failure, like compliance, pharmacological factors, including poor bioavailability, wrong dose regimens, lack of adherence to drug intake, neglect of partner notification and concomitant therapy in consorts, possible development of resistance to drugs generally prescribed, false negative or false positive diagnostic tests and reinfection from extra-genital not 'cured' sites. The review points to the need to establish programmes for routine rescreening of chlamydia-infected persons.

Microscopy of stained smears of vaginal secretion in the diagnosis of recurrent vulvovaginal candidosis.

This study was undertaken to determine the value of stained smears from the vaginal introitus and the posterior vaginal fornix for detection of candida morphotypes in the diagnosis of recurrent vulvovaginal candidosis (RVVC) in cases with an assumed novel attack of the condition, and to compare the value of microscopy of such smears in relation to candida culture, vaginal pH-determinations and leucocyte esterase tests (LE). One hundred and thirteen women with a history and a current assumed attack of RVVC were studied by means of culture of samples from the vaginal introitus and posterior vaginal fornix on Sabouraud and CHROMagar. Microscopy of methylene blue- and Gram-stained smears from these sites was performed. The pH of vaginal secretion and the LE activity in vaginal flushing fluid was measured. Candida morphotypes were found significantly more often in the smears from candida culture-positive than culture-negative women. There was no difference in this respect between the findings in the methylene blue- and Gram-stained smears. Differences were found in candida morphotypes among Candida albicans and non-albicans-positive cases, as blastoconidia were detected only in the latter cases. The leukocyte esterase activity score was higher in the candida-positive than in candida-negative cases. The study showed that microscopy of fixed, stained genital smears can play a role in attempts to distinguish cases infected and not infected by candida among patients consulting with an assumed novel attack of RVVC. Study of methylene blue-stained smears is recommended as they represent an easier means than Gram-stained smears to diagnose genital candida infections in assumed RVVC cases.

Detection of candida by polymerase chain reaction vs microscopy and culture in women diagnosed as recurrent vulvovaginal cases.

The objectives were to compare the outcome of polymerase chain reaction (PCR), culture and microscopy of introital and vaginal samples for detection of candida in women with a history of recurrent vulvovaginal candidosis (RVVC). One hundred and three women with a history of RVVC, i.e. with at least four episodes of the condition in the previous year and who consulted with complaints consistent with a new episode, were studied. Introital and vaginal swabs were cultured on Sabouraud and CHROMagar. Isolated strains were identified on the chromogenic agar and by API 32C kits and by Vitek automatized identification system (BioMérieux, France). PCR for detection of Candida spp. was performed on vaginal lavage fluid. There was a complete agreement in the recovery rate when using the two agar media. However, complete concordance was not obtained between culture and PCR. In 32 (43.8%) of 73 women both PCR and culture were positive, and in 17 (23.3%) both were negative. In 15 (20.5%), only cultures proved positive, while in another 13 (17.8%) patients only the PCR was positive. Four of the PCR-negative became PCR-positive on retesting after dilution of the sample to try to reduce any potential putative PCR inhibitors. In the 47 PCR-positive women, 26 (55.3%) of the introital smears and 31 (65.9%) posterior vaginal smears showed candida morphotypes. In the 25 PCR-negative women, the corresponding figures were 9 (36.0%) and 17 (68.0%), respectively. The PCR test identified Candida albicans in 21 (87.5%) instances, but failed to do so in three (12.5%) cases in which the metabolic/assimilation tests were positive for this species. The corresponding figures for non-albicans Candida spp. were four (57%) and three (43%), respectively. The study of women with RVVC did not show any uniform agreement between the different diagnostic methods used to identify candida in genital samples or for speciation of yeast isolates. Thus reliance only on microscopy, culture or PCR may lead to inaccurate results.

Facts and myths on recurrent vulvovaginal candidosis--a review on epidemiology, clinical manifestations, diagnosis, pathogenesis and therapy.

Approximately three-quarters of all women will experience an episode of vulvovaginal candidosis at least once in their life and 5-10% of them will have more than one attack. Women suffering from three to four attacks within 12 months will be diagnosed with recurrent vulvovaginal candidosis (RVVC). This review covers the large number of proposed aetiological factors for RVVC. The diagnosis of the condition made by conventional means by health providers is often false and is also often misdiagnosed by the affected woman herself. The review covers various methods of diagnosing RVVC and the current knowledge on potential pathogenetic mechanisms proposed for genital candida infections. Treatment of RVVC, including local and systemic antimicrobial therapy and behaviour modification to decrease the risk of recurrences, are discussed. Recent knowledge on drug resistance in candida is also included.

Mannan-binding lectin in women with a history of recurrent vulvovaginal candidiasis.

OBJECTIVES: To determine the serum concentration of mannan-binding lectin (MBL), a component of the innate immune system, in women with a history of recurrent vulvovaginal candidiasis (RVVC) and to correlate the result to candida-cultures, contraceptive use, if any, and to different antifungal therapies. STUDY DESIGN: Twenty-nine women with a history of RVVC were investigated. Cultures of vulvar and vaginal samples were grown on chromogenic agar. Serum levels of MBL were determined by a sandwich time-resolved immunofluorometric assay, using anti-MBL coated microtiter wells containing samples, which were washed, incubated with biotinylated anti-MBL followed by europium-labeled streptavidin and measured by time-resolved flourometry. RESULTS: The median MBL level was higher in the RVVC cases than in 30 women with no history of genital candida infection who served as a comparison group (p=0.006). It was also higher in the candida-positive than in the culture-negative RVVC (p=0.02). The median concentration of MBL was also higher in hormonal contraceptive users as compared to condom-users and those using no contraceptive at all (p=0.03). CONCLUSION: The result indicates a role of MBL in RVVC and the production may correlate to vulvar/vaginal colonization by Candida, hormonal contraceptive use, and antifungal therapies.

Aetiology, diagnosis and therapy of sexually transmitted and allied infections--reflections on novel observations and current trends.

The present communication highlights aspects on the aetiology, diagnosis and therapy of sexually transmitted infections (STIs) and some allied infections in which sexual transmission is regarded as possible. The aetiology of many genital infections is still unknown or rather, an aetiological relationship between a given agent and a clinical manifestation is in some infections still debated. The paper will discuss some shortcomings in the current surveillance systems for STIs, if these systems exist at all. Thus, the paper considers their value in estimating the extent of the problem on a general population basis. It also focuses on the discrepancy between the current high prevalence of diagnosed cases of some STIs, such as of genital chlamydia infections, and the relatively low number of complications and sequelae presently seen, in contrast to the comparatively high prevalence more commonly reported in the past. Recent discoveries of novel aetiological agents of STIs, including mycoplasmas, may explain a lack of recovery from infections, due to the common use of antibiotic drugs to which these agents have a natural resistance. The observation of a synergistic effect of a commonly used anti-inflammatory drug, which may overcome antifungal resistance in vulvovaginal candidiasis, will also be reviewed. Furthermore, other reflections concern some of the classic STIs, e.g. lymphogranuloma verenerium, syphilis, gonorrhoea, herpes and condyloma.

Female genital mutilation -- an exported medical hazard.

BACKGROUND: Female circumcision (FC) has remained a common practice in the countries where it has traditionally been performed. Following increased global mobility, it has also become a common medical issue in the predominantly non-Islamic countries where an increasing number of immigrants from regions where FC is still traditional, have settled. OBJECTIVES: To investigate types of FC found in a group of immigrants from northern Africa with a current domicile in Scandinavia. To characterize these women with regard to education, socio-economic status and experienced complications and sequelae. To report attitudes to FC among the women and their husbands. METHODS: An autoquestionnaire was distributed to 220 immigrant women (16-42 years old), who belonged to an African community in Scandinavia and who had all been circumcised. Information was also gathered concerning 76 of their daughters (aged 1-13 years). Of the women's husbands, 95 were asked about their attitudes to FC. RESULTS: Of the 140 women, who had been circumcised in their home country before they migrated, 78 (35%) had been clitoridectomized, 38 (17%) had been subjected to genital excision and 24 (11%) to infibulation. The corresponding percentages in the remaining women, who had had FC when returning home for a visit, were 0%, 14% and 22%, respectively. Of the daughters, 15 (19%) had been circumcised whilst living in Scandinavia; all had been clitoridectomized. Twenty-eight (13%) women reported having experienced late complications or post-FC sequelae. A positive attitude to stopping the tradition of FC was reported twice as often by the husbands (69%) as by the circumcised women (35%). Religion (95% of the responders were Muslims and 5% Christians), cultural tradition, and increased chance of marriage or of continued health were the reasons put forward in favor of the continuation of FC by 58%, 27%, 10% and 4 %, respectively. Five per cent could not supply an opinion. CONCLUSIONS: FC is performed in immigrant women even after settling in areas where this practise is legally banned. Circumcised immigrant women experience medical and sexual problems which have to be dealt with in their new domicile country. Many African Islamic women, who have migrated to Scandinavia, seem still to be in favour of the continuation of circumcision for varying reasons.

Potent synergic effect between ibuprofen and azoles on Candida resulting from blockade of efflux pumps as determined by FUN-1 staining and flow cytometry.

OBJECTIVES: Resistance to antifungals often relates to efflux pumps exporting drugs; several modulators may block them, reverting resistance. Verapamil, beta-oestradiol and progesterone, known efflux pump inhibitors of human neoplastic cells, and ibuprofen were tested as potential modulators of resistance of Candida spp. METHODS: Forty-two clinical isolates of Candida (38 fluconazole-resistant), two ATCC type strains and two C. albicans strains with known mechanisms of fluconazole resistance were incubated with subinhibitory concentrations of the modulators. After exposure, MICs of fluconazole, itraconazole and voriconazole were re-determined. Simultaneously, yeasts exposed to modulators were stained with FUN-1 and analysed by flow cytometry. 3H-labelled itraconazole was also used to study efflux in the presence and absence of modulators. RESULTS: Fluconazole MICs decreased in most strains after exposure to modulators, including control strains with documented efflux overexpression. No significant MIC variation was noticed for: all C. krusei strains tested, for the resistant strain by target change, for susceptible strains, and for a very few other clinical isolates. Reverted resistant phenotypes showed cross-resistance to itraconazole and to voriconazole, which was also reverted by the modulators. For these strains, an increase in FUN-1 staining and increased accumulation of 3H-labelled itraconazole were noticed after incubation with modulators. CONCLUSIONS: Resistance related to overexpression of efflux pumps was common among clinical isolates and could be reverted by the assayed modulators, particularly ibuprofen. The mechanism of resistance in all tested C. krusei and in a few other strains seems, however, to be of a different nature. Ibuprofen is a promising compound in association with azoles, deserving future clinical trials. FUN-1 proved to be a good marker of efflux in Candida.

Tubal factor infertility, with special regard to chlamydial salpingitis.

PURPOSE OF REVIEW: This article will highlight recent research into tubal factor infertility as one of the main causes of involuntary childlessness in women. There will be a focus on chlamydial infections. RECENT FINDINGS: The most common cause of tubal factor infertility is occlusion of the fallopian tubes due to an infection by a sexually transmitted agent, by Chlamydia trachomatis or Neisseria gonorrhoeae. The prevalence of diagnosed cases of tubal factor infertility (TFI) can be correlated to the epidemiological situation regarding these agents that was prevailing several years ago. This is partly due to the trend seen in many Western countries that women often postpone to try to get pregnant. Therefore, there is often a time lag between the acute primary pelvic inflammatory disease (PID) and when women first consult because of fertility problems. Sub-clinical salpingitis is today regarded as even more common than symptomatic PID. Persistent tubal infections by C. trachomatis are also a common feature, even despite courses of antibiotic therapy. The current focus on TFI has been on the immunopathology of tubal chlamydial infections, for which differences in host factors, such as genetic polymorphism in cytokine response and human leukocyte antigen type, may play a role in the outcome of pelvic inflammatory disease. Hysterosonography is a more convenient mode for diagnosing tubal occlusion than hysterosalpingography. The use of new species-specific antibody tests for C. trachomatis has decreased previous specificity problems found when used to detect tubal occlusion in work-up of women consulting because of infertility. SUMMARY: Infection by C. trachomatis is a major cause of TFI. Many cases of chlamydial salpingitis have a more or less subclinical course. The tubal infection may become chronic in spite of antibiotic therapy. Immunological processes may continue after microbiological cure, which stresses the importance of screening for C. trachomatis in order to detect and treat carriers to hinder spread to still uninfected women.

Characterization of women with a history of recurrent vulvovaginal candidosis.

BACKGROUND: To characterize history, signs, and symptoms in women with a history of recurrent vulvovaginal candidosis (RVVC) and who had consulted with symptoms generally associated with the condition. METHODS: Eighty-three women with a history consistent with RVVC were interviewed regarding 32 parameters and 10 signs found at the clinical examination were noted. Candida cultures were made from the introitus and the posterior vaginal fornix. RESULTS: Only in a few of the 43 women with and the 40 without a positive yeast culture could any of the many etiological factors that have been associated with RVVC be traced. Only two factors differed between the groups, namely yogurt intake, which was reported by 28 (68%) and 38 (95%) women in these groups, respectively. Vaginal douching was performed by 10 (23%) women in the Candida-positive group and by 17 (42%) women in the Candida-negative group. Pruritus and burning occurred in 31 (72%) and 22 (51%) of culture-positive patients, which was less frequent than in the culture-negative group, i.e. reported by 19 (47%) and 9 (22%) patients, respectively (p = 0.022 and p = 0.007). Edema (p = 0.026) of the vulva as well as erythema (p = 0.019) and edema (p = 0.008) of the vaginal mucosa, caseous discharge (p = 0.016), were found more often in the Candida culture-positive cases. CONCLUSIONS: History and results of clinical examination of patients with RVVC are not enough to distinguish those who are culture-positive from those who are culture-negative for Candida from the genital tract.

Colonisation of extragenital sites by Candida in women with recurrent vulvovaginal candidosis.

OBJECTIVES: To study colonisation of extragenital sites by Candida in women with a history of recurrent vulvovaginal candidosis and to determine the association of such colonisation with clothing and sexual practice. DESIGN: A prospective case-control (current genital colonisation by candida organisms vs non-colonisation) study. SETTING: Outpatient clinic, University hospital, Kiev, Ukraine and Department of Obstetrics and Gynaecology, University Hospital, Lund, Sweden. SAMPLE: Women with a history of recurrent vulvovaginal candidosis and an assumed new attack of the condition. METHODS: Eighty-six women with a history of recurrent vulvovaginal candidosis and an assumed current attack of this condition underwent culture for Candida from the genital tract, the perianal skin, the rectum, the mouth and from voided urine samples, using Sabouraud and chromogenic agar. The women were interviewed about some factors that have been considered to trigger colonisation with Candida spp. MAIN OUTCOME MEASURES: Colonisation of extragenital sites of women with recurrent vulvovaginal candidosis by different species of Candida. Correlation with oral and anal sex, and with clothing. RESULTS: Candida spp. was isolated from the mouth, the rectum, the perianal skin and from voided urine in 11(13%), 24(28%), 35(41%) and 16(19%) of women, respectively. Candida was recovered from one or more of these sites in 44(51%) of the women. The rate of culture of Candida from the extragenital sites was significantly higher (P < 0.05) in women who had a positive culture from the introitus or the vagina. The recovery rates of Candida in the 46 vaginal culture-positive women were 8 (17%), 24 (52%), 34 (74%) and 16 (35%) from the extragenital sites in the order mentioned. Species of Candida other than Candida albicans occurred more often at the extragenital than the genital sites. Neither oral nor anal sex was associated with colonisation of the mouth and the rectum with Candida spp. Neither tight-fitting trousers nor underwear produced from synthetic material was associated with colonisation of the perianal skin with Candida spp. CONCLUSIONS: Extragenital sites are often colonised by Candida spp. in women with a history of recurrent vulvovaginal candidosis, but significantly more often if the genital tract is also colonised. Extragenital sites are significantly more commonly colonised with species other than C. albicans. Extragenital sites may be reservoirs for recolonisation of the genital tract in women with recurrent vulvovaginal candidosis. This has implications for treatment.

Usage of antifungal drugs for therapy of genital Candida infections, purchased as over-the-counter products or by prescription: I. Analyses of a unique database.

OBJECTIVES: To present sales figures of antifungal drugs for treatment of genital Candida infections in females, which had been purchased in the Swedish county of Skåne (with approximately 1.2 million inhabitants) during the 1990s. To study the relative proportions of the drugs sold by prescription and as over-the-counter (OTC) products. METHODS: Sales figures of antifungal drugs for therapy of vulvovaginal candidiasis (VVC) and such recurrent infections (RVVC), for the years 1990--99, were collected from the 'ACS' database of the National Corporation of Swedish Pharmacies. RESULTS: The study showed an increase in sales of the type of drugs studied from 45,000 packages in 1990 until mid-93/94, when approximately 70,000 packages were sold (mainly azoles for topical use and fluconazole for oral intake). Thereafter there was a decrease until the end of November 1999, when 54,000 packages were purchased. Of the total sales, 93% were OTC products. Sales of clotrimazole and econazole (for vaginal installation) in 1993--1994 were equal to 85-90 packages/1000 women in the age group 15-45 years. Extremely high sales volumes of fluconazole and itraconazole, for one single year each, could be explained by marketing-related activities directed to the medical community. CONCLUSIONS: As many women with RVVC are not cured by iatrogenic initiatives and women consider themselves able to diagnose episodes of genital Candida infection, affected women generally turn to self-medication with antifungal OTC products. This stresses the role of pharmacy counseling. Short-term marked alterations in sales volumes may be due to marketing factors rather than changes in the epidemiology of genital Candida infections.