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.

Clinical results and concentrations of cefmenoxime in serum, amniotic fluid, mother's milk, and umbilical cord.

Cefmenoxime administered intravenously was used to treat a variety of gynecologic and obstetric infections in 40 patients. Many were mixed infections. The mean age of the patients was 39.7 +/- 2.39 years. The dosage of cefmenoxime was 2 g per day (n = 30) or 1 g per day (n = 10). Cefmenoxime levels were assayed microbiologically in serum, milk, amniotic fluid, and placental tissues. The overall bacteriologic cure rate was 86 percent. Clinically, 100 percent of the patients were treated successfully. Side effects were generally mild, and in no case was treatment discontinued. Twelve hours after the last bolus injection, levels of cefmenoxime were 1.1 microgram/ml in serum and 1.75 microgram/ml in milk. Thirty minutes after a 1 g bolus injection in patients undergoing cesarean section, mean maternal serum concentrations were 33 micrograms/ml. Concentrations were 7.4 micrograms/ml in umbilical cord blood and 2.3 micrograms/ml in amniotic fluid.

Temocillin treatment of gynaecological infections with special reference to blood and tissue concentrations.

Tissue concentrations of temocillin were determined in samples from gynaecological surgical patients. Measurable concentrations of temocillin were observed during the entire time period investigated (up to 7 hours post administration). Inhibitory concentrations for the majority of susceptible bacteria were achieved. The therapeutic results observed in 40 patients with various infections (90% fully effective, 5% partially effective) confirm the high efficacy of temocillin in the treatment of gynaecological infections.

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.

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.

[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.

[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.

[Candidiasis of vagina and anus among women (author's transl)]. / Zum Hefebefall des weiblichen Urogenitales und des Anorektalbereichs.

From 566 patients who attended a special clinic for diagnosis and treatment of vaginal fluor 1698 smears from urethra, vagina, and anus were taken. In 121 cases Candida was found. In 16 out of 111 patients (14%) the fungus was isolated only from the ano-rectal area. A rectal smear is very essential in case of suspected candidiasis. It should be done in general practice if a recurrence of the infection is observed or if the candidiasis appears resistant to treatment.

[Mycoplasms in the anorectal region of women (author's transl)]. / Uber das Vorkommen von Mykoplasmen im Anorektalbereich der Frau.

650 samples of vaginal and anorectal smear from 325 women with fluor were examined. 78 patients (24%) had mycoplasms. 17% of these patients had only rectal mycoplasms and 30.5% women had only vaginal mycoplasm. 51.3% of the women had fluor since years, they had mycoplasms as well in the rectal as in the vaginal region. There were urea cracking and non urea cracking mycoplasms.

[Studies on the colonization of female urogenital system by Mycoplasma]. / Untersuchungen über die Besiedelung des weiblichen Urogenitale mit Mykoplasmen

In order to demonstrate a urogenital mycoplasmosis, restriction is made frequently also in women - to withdrawal of smear from the urethra. For recognizing whether this procedure is sufficient, 640 female patients of the fluor consulting hours were examined, and 2560 smears were withdrawn from the cervical canals, the surface of the portio, the laterovaginal walls, and from the urethra. The least frequency of mycoplasmas was stated in the urethra. Smears merely withdrawn from the urethra are, therefore, the least appropriate ones for fluor or for identification of a urogenital mycoplasmosis of the female genitals. According to the present results, it is recommended to carry out simultaneously smears from the surface of the portio, from the laterovaginal walls, as well as from the cervical canal and the urethra.

[Investigation on the mycoplasma population of the lochia (author's transl)]. / Untersuchungen zur Besiedelung des Lochialsekretes mit Mykoplasmen.

105 puerperae were examined for mycoplasma population one day and seven days post partum, after pregnancy and childbirth had remained without any complications. Whereas mycoplasmas could be identified in the lochia of 10 women in the seventh day post partum, all mycoplasma investigations remained negative on the day following childbirth.

[Investigations on mycoplasma infestation of the human placenta post partum (author's transl)]. / Untersuchungen zum Mykoplasmenbefall der menschlichen Plazenta post partum.

In 95 healthy delivered women the placenta (externally and internally) and the amniotic sac were examined for mycoplasma population. Mycoplasmas could not be identified in any of the cases under investigation. In healthy pregnant women, mycoplasmas are not identifiable as "harmless commensals" either in the amniotic sac or in the placenta. In cases where mycoplasmas are found, they may act as pathogens.

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.