IL-23, IFN-α, and IFN-ß in the vaginal fluid of patients suffering from vulvovaginal candidosis.

Purpose of the investigation: Vulvovaginal candidosis (VVC) is a common vaginal infection affecting almost 75% of all women once per lifetime. Vaginal associated immunity is important in the protection against VVC. The purpose of this study was to evaluate a potential role of IL-23, IFN-α, and IFN-ß in the local immune response against VVC. MATERIALS AND METHODS: The study included 202 non-pregnant women; 71 patients with clinical symptoms of VVC and 131 asymptomatic patients served as control. IL-23, IFN-α, and IFN-ß were measured in the vaginal fluid by ELISA. Microbiological cultures were used for Candida detection. RESULTS: C. albicans was detected in 67.6% of patients, C. glabrata in 2 1.1% of patients, and 5.6% were infected with C. krusei or coinfected with C. albicans and C. krusei. Levels of IL-23 (p < 0.001) and IFN-ß (p < 0.017) were significantly lower in the VVC group. IFN-α was elevated in the VVC group compared to the asymptomatic patients (p < 0.001). CONCLUSION: IL-23 and IEFN-ß seem to play a protective role against VVC. Decreased levels in VVC patients suggest a compromised local immune response at the time of occurrence of symptoms. In contrast, IFN-α seems to be released once the infection has occurred. These cytokines may be prospective targets in the treatment and prevention of primary and recurrent vaginal infections with Candida species.

Guideline: vulvovaginal candidosis (AWMF 015/072), S2k (excluding chronic mucocutaneous candidosis).

The oestrogenised vagina is colonised by Candida species in at least 20% of women; in late pregnancy and in immunosuppressed patients, this increases to at least 30%. In most cases, Candida albicans is involved. Host factors, particularly local defence mechanisms, gene polymorphisms, allergies, serum glucose levels, antibiotics, psycho-social stress and oestrogens influence the risk of candidal vulvovaginitis. Non-albicans species, particularly Candida glabrata, and in rare cases also Saccharomyces cerevisiae, cause less than 10% of all cases of vulvovaginitis with some regional variation; these are generally associated with milder signs and symptoms than normally seen with a C. albicans-associated vaginitis. Typical symptoms include premenstrual itching, burning, redness and odourless discharge. Although itching and redness of the introitus and vagina are typical symptoms, only 35-40% of women reporting genital itching in fact suffer from vulvovaginal candidosis. Medical history, clinical examination and microscopic examination of vaginal content using 400× optical magnification, or preferably phase contrast microscopy, are essential for diagnosis. In clinically and microscopically unclear cases and in chronically recurring cases, a fungal culture for pathogen determination should be performed. In the event of non-C. albicans species, the minimum inhibitory concentration (MIC) should also be determined. Chronic mucocutaneous candidosis, a rarer disorder which can occur in both sexes, has other causes and requires different diagnostic and treatment measures. Treatment with all antimycotic agents on the market (polyenes such as nystatin; imidazoles such as clotrimazole; and many others including ciclopirox olamine) is easy to administer in acute cases and is successful in more than 80% of cases. All vaginal preparations of polyenes, imidazoles and ciclopirox olamine and oral triazoles (fluconazole, itraconazole) are equally effective (Table ); however, oral triazoles should not be administered during pregnancy according to the manufacturers. C. glabrata is not sufficiently sensitive to the usual dosages of antimycotic agents approved for gynaecological use. In other countries, vaginal suppositories of boric acid (600 mg, 1-2 times daily for 14 days) or flucytosine are recommended. Boric acid treatment is not allowed in Germany and flucytosine is not available. Eight hundred-milligram oral fluconazole per day for 2-3 weeks is therefore recommended in Germany. Due to the clinical persistence of C. glabrata despite treatment with high-dose fluconazole, oral posaconazole and, more recently, echinocandins such as micafungin are under discussion; echinocandins are very expensive, are not approved for this indication and are not supported by clinical evidence of their efficacy. In cases of vulvovaginal candidosis, resistance to C. albicans does not play a significant role in the use of polyenes or azoles. Candida krusei is resistant to the triazoles, fluconazole and itraconazole. For this reason, local imidazole, ciclopirox olamine or nystatin should be used. There are no studies to support this recommendation, however. Side effects, toxicity, embryotoxicity and allergies are not clinically significant. Vaginal treatment with clotrimazole in the first trimester of a pregnancy reduces the rate of premature births. Although it is not necessary to treat a vaginal colonisation of Candida in healthy women, vaginal administration of antimycotics is often recommended in the third trimester of pregnancy in Germany to reduce the rate of oral thrush and napkin dermatitis in healthy full-term newborns. Chronic recurrent vulvovaginal candidosis continues to be treated in intervals using suppressive therapy as long as immunological treatments are not available. The relapse rate associated with weekly or monthly oral fluconazole treatment over 6 months is approximately 50% after the conclusion of suppressive therapy according to current studies. Good results have been achieved with a fluconazole regimen using an initial 200 mg fluconazole per day on 3 days in the first week and a dosage-reduced maintenance therapy with 200 mg once a month for 1 year when the patient is free of symptoms and fungal infection (Table ). Future studies should include Candida autovaccination, antibodies to Candida virulence factors and other immunological experiments. Probiotics with appropriate lactobacillus strains should also be examined in future studies on the basis of encouraging initial results. Because of the high rate of false indications, OTC treatment (self-treatment by the patient) should be discouraged.

Relationship between clinical diagnosis of recurrent vulvovaginal candidiasis and detection of Candida species by culture and polymerase chain reaction.

BACKGROUND: Recurring vulvovaginal candidiasis (RVVC) is a common vaginal discharge affecting 75% of all women at least once in their life. In 5% of these women, infection is recurring. Aim of the study was to determine the sensitivity of detecting Candida species by culture and polymerase chain reaction (PCR) in women with a clinical diagnosis of RVVC. METHODS: A total number of 104 patients referred with a clinical diagnosis of RVVC and therefore at least four episodes in the previous year were evaluated. In order to detect Candida, vaginal swabs were cultured on Sabouraud and chromagar. Furthermore, the supernatant from the vaginal lavage was examined for the presence of Candida by PCR. RESULTS: When the culture was analyzed, only 31 (29.8%) of the 104 patients diagnosed with RVVC were positive for Candida species in their vagina. Candida albicans was identified in 25 women and six were positive for Candida glabrata. When analyzed by PCR, 44 (42.3%) patients were positive for Candida species. In 13 women (12.5%) only the PCR was positive, while in 31 patients both culture and PCR were positive. CONCLUSION: The diagnostic method of PCR is more sensitive than culture in detecting Candida species in the vagina. The results also suggest further investigation to verify the complaints of the negative tested patients.

Evidence of a TH1-shift of local vaginal inflammatory response during bacterial vaginosis.

OBJECTIVE: To determine the levels of pro-inflammatory and anti-inflammatory cytokines in the vagina of healthy women and in bacterial vaginosis (BV) patients. METHODS: Interleukin (IL)-1alpha, 1beta, 5 and 10 were analyzed by ELISA in vaginal wash fluids from 50 non-pregnant patients with BV and 112 healthy women. RESULTS: Levels of IL-1beta were higher and those of IL-10 lower in BV-patients than in healthy women. There was a tendency towards higher levels of IL-1alpha in BV patients, but these data were not statistically significant. CONCLUSION: We found evidence for a shift towards a TH1-dominated vaginal cytokine profile in the pathogenesis of BV. Levels of a TH1-cytokine were elevated and those of a TH2-cytokine lowered in BV-patients as compared to healthy controls. This points to a vaginal TH1-response during BV and to the importance of cell-mediated immunity in local vaginal infections.

[Chlamydia trachomatis infections--a time for action?]. / Chlamydia-trachomatis-Infektionen--Zeit zum Handeln?

Infection with Chlamydia trachomatis is the most common sexually transmitted disease in the world. In women it mainly occurs before the age of 25 years, while in men it can still be diagnosed till the age of 35 years. In Western Europe the prevalence of a Chlamydia trachomatis infection has been estimated, according to WHO data, as between 2.7% (Italy) and 8.0% (Island). A general screening strategy is now being discussed in Germany. A non-diagnosed and non-treated Chlamydia trachomatis infection and the resulting health problems have not only severe consequences for the individual but also results in major epidemiological and socio-economic public health problems. This issue is not only of extreme importance in health policy, but has also a major impact in family policy, especially in view of the declining birth rates and the demographic changes.

[Parvovirus B 19 infection during pregnancy]. / Parvovirus-B 19-Infektion in der Schwangerschaft.

The parvovirus B 19 is part of the family of the parvoviridae and shows a distinctive tropism for erythropoid precursor cells. The virus causes in children the erythema infectiosum (German measles). Meanwhile, parvovirus B 19 infections can be associated with a wide spectrum of hematological and non-hematological complications (e.g. liver failure, hepatitis, aplastic crises primarily in association with chronic hemolytic anaemias, chronic arthritis, arthralgia/arthritis, transient/persistent anaemias, vasculitis, glomerulonephritis). Intrauterine infections can lead to specific or permanent organ defects (e.g. heart anomalies, eye diseases, micrognathy, chronic anaemia, myocarditis, hepatitis, mekonium peritonitis and central nervous system anomalies). Parvovirus B 19 infections are also associated with hydrops fetalis and intrauterine death during pregnancy. A definite relation between fetal malformations and B 19 infection has not been accomplished yet. Pregnancies complicated by parvovirus B 19 infection should be followed for further exclusion of any teratogenic effect. Although congenital malformations after a parvovirus infection are possible, this phenomenon seems to be rare. An intrauterine therapy with packed red cells could be performed for hydrops fetalis and low haemoglobin concentration. Investigation for the development and clinical testing of an efficient vaccine against parvovirus B 19 is currently in progress.

[The significance of interleukins and of Candida-IgE in chronic recurrent vulvovaginal candidosis]. / Die Bedeutung der Interleukine und des Candida-IgE bei der chronisch rezidivierenden Vulvovaginalcandidose.

We examined 104 patients with chronic recurrent vulvovaginal candidosis; 41 healthy women were selected for the control group. Vaginal samples were taken, and yeasts were grown and tested for Candida strains: 29.8% of samples contained Candida spp.; two of the control women were infected. We also identified interleukin IL-4, 5 and 13, but there was only significant increase in IL-4. In addition, prostaglandin E2, whole IgE and Candida-specific-IgE was identified. Also here prostaglandin E2 and the Candida IgE were significantly higher in comparison with the control group, while whole IgE showed no significant increase. This resulted in an allergic component in the chronic recurrent vulvovaginal candidosis, which suggested that therapy should be reconsidered.

Value of Candida polymerase chain reaction and vaginal cytokine analysis for the differential diagnosis of women with recurrent vulvovaginitis.

OBJECTIVES: Recurrent vulvovaginitis remains difficult to diagnose accurately and to treat. The present investigation evaluated the utility of testing vaginal specimens from women with symptomatic recurrent vulvovaginitis for Candida species by polymerase chain reaction (PCR) and for cytokine responses. METHODS: Sixty-one consecutive symptomatic women with pruritus, erythema, and/or a thick white discharge and a history of recurrent vulvovaginitis and 31 asymptomatic women with no such history were studied. Vaginal swabs were tested for Candida species by PCR, for the antiinflammatory cytokine interleukin (IL)-10, and for the proinflammatory cytokine IL-12. RESULTS: C. albicans was detected in 19 (31.1%) of the patients as well as in three (9.7%) controls (P = 0.03). Both IL-10 (31.1% vs. 0%) and IL-12 (42.6% vs. 6.5%) were also more prevalent in the recurrent vulvovaginitis patients (P < 0.001). However, there was no relation between the presence or absence of Candida and either cytokine. Detection of IL-12 in 14 women indicated the stimulation of a vaginal cell-mediated immune response possibly from an infectious agent. The presence of only IL-10 in six patients indicated a suppression of vaginal cell-mediated immunity and was consistent with a possible allergic etiology. The absence of both IL-10 and IL-12 in other patients, similar to that found in healthy controls, suggested a noninfectious, nonallergic etiology of their symptoms. CONCLUSION: Many women with recurrent vulvovaginitis are not infected with Candida. Testing for Candida should be required in this population. Treatment with only anti-Candida medication will clearly be inadequate for the majority of women with this condition.

Placental passage of angiotensin-converting enzyme inhibitors.

OBJECTIVE: Placental passage of the angiotensin-converting enzyme inhibitors temocapril and enalapril was investigated in a placental perfusion model. STUDY DESIGN: In an open system a placental lobe was perfused on both the maternal and the fetal side with a blood-free medium containing the test substances plus a reference substance on the maternal side. Six placentas were perfused with temocapril and five with enalapril. The drugs were measured by gas chromatography-mass spectrometry. RESULTS: Both angiotensin-converting enzyme inhibitors crossed the human placenta in the maternal-fetal direction in similar quantities. Temocapril showed the same pharmacokinetic characteristics as enalapril. CONCLUSIONS: This was the first study to quantify the placental transfer of angiotensin-converting enzyme inhibitors. These antihypertensive agents should not be taken during pregnancy, to avoid any potential hazards to the fetus.

Efficacy of clindamycin vaginal cream versus oral metronidazole in the treatment of bacterial vaginosis.

OBJECTIVE: To compare the efficacy and tolerance with 2% clindamycin vaginal cream versus oral metronidazole for the treatment of bacterial vaginosis. METHODS: This was a multicenter, randomized, double-blind study in which patients were randomly assigned to one of the following two regimens in a 1:1 ratio: clindamycin phosphate vaginal cream 2% (5 g intravaginally at bedtime for 7 days) plus two placebo capsules (twice a day for 7 days) or metronidazole 500 mg (two 250-mg capsules orally twice a day for 7 days) plus placebo vaginal cream (5 g intravaginally at bedtime for 7 days). The patients were seen for follow-up at 5-10 days and 25-39 days after completion of therapy. RESULTS: Seven investigators, four in Germany, two in Austria, and one in Switzerland, enrolled 407 patients. Four patients never received either protocol drug, leaving 403 evaluable for safety. Two hundred thirty-four patients were evaluable for efficacy. The analysis for all evaluable patients showed no significant difference between treatment groups. The cure or improvement rate at 1 month after therapy was 83% in the clindamycin group versus 78% in the metronidazole group. The incidence of drug-related adverse medical events was approximately 12% in both groups. CONCLUSIONS: Oral metronidazole and intravaginal clindamycin cream had a similar efficacy of 78 to 83%. Both drugs were tolerated, with vaginal candidiasis developing in 8.5 and 4.7% of the patients in the clindamycin and metronidazole groups, respectively.

Uncomplicated urinary tract infections in pregnant and non-pregnant women.

Urinary tract infections (UTIs) are still one of the most common bacterial infections in pregnant and non-pregnant women. It is estimated that about 10-20% of all women suffer from a UTI at some point in life. The presence of UTI is defined as the existence of urinary symptoms such as frequency of urination and dysuria with or without bacteriuria or pyuria. The prevalence of bacteriuria in females varies from less than 1% in infants to 10% and more in older women. There are major differences in the clinical features between young and elderly women depending on the different pathogenesis, microbiology and general condition. Especially for elderly women, symptomatic and asymptomatic bacteriuria presents a risk factor for bacteraemia, sepsis and also increased mortality. During pregnancy, the prevalence of bacteriuria does not change but there are some changes in the pathogenesis that increase the rate of pyelonephritis. Asymptomatic bacteriuria rarely resolves spontaneously during this time. For non-pregnant women, short therapy strategies are recommended, preferably 3 days of trimethoprim-sulphamethoxazole (TMP/SMX) or quinolones. In pregnant women, therapy with amoxycillin or an oral cephalosporin is considered optimal.

[Problem infections of the external genital area in the female]. / Probleminfektionen des äusseren Genitalbereiches der Frau.

On account of difficult diagnostic procedures and often atypical clinical pictures, the following diseases must be regarded as problematic infections: infections with chlamydia, mycoplasma, urea-plasma, and herpes virus, as well as unspecific infections with aerobic and anaerobic bacteria. Since vulvitis and vaginitis are frequently associated with vaginal discharge, they may present a problem to dermatologists and gynecologists.

[Interstitial and intramural pregnancy--definition and sonographic references]. / Interstitielle und intramurale Gravidität--Begriffsbestimmung und sonographische Hinweiszeichen.

Two cases of atypical implantation are presented in order to illustrate the difference between interstitial and intramural pregnancy. Ultrasonography can provide a method of early diagnosis of heterotypic sitting before the occurrence of clinical symptoms. In cases where complications already occurred, sonography can be used to confirm the clinical diagnosis.