P. Giraldo

Vaginal colonization by Candida in asymptomatic women with and without a history of recurrent vulvovaginal candidiasis.

Objective The asymptomatic carriage of Candida in the vagina of women with a history of recurrent vulvovaginal candidiasis was compared with that of women with no such history. Methods Vaginal swabs from 50 women with a history of recurrent vulvovaginal candidiasis and 45 women with one or fewer episodes of candidal vaginaitis within the past 12 months were evaluated for Candida by wet mount/Gram stain, culture, and polymerase chain reaction (PCR). All women were asymptomatic for at least 30 days. Results Candida was identified in 28 women by PCR, in 14 women by culture, and in 13 women by wet mount/Gram stain. Candida was identified by PCR in a similar proportion of patients with previous recurrent vulvovaginal candidiasis (30%) and in controls (28.8%). However, Candida was identified by culture in more women with previous recurrent vulvovaginal candidiasis (22%) than in controls (6.6%, P = .04); it also was identified by wet mount/Gram stain in more women with recurrent vulvovaginal candidiasis (22%) than in controls (4.4%, P = .01). For the recurrent vulvovaginal candidiasis patients, culture and wet mount/Gram stain had a sensitivity of 66.6% compared with PCR. For the controls, the sensitivity of the two former assays relative to PCR was only 15.3%. Conclusion Women with a history of recurrent vulvovaginal candidiasis have more easily detectable Candida in their vagina, even when asymptomatic, than do other women. A relative inefficiency in regulating the proliferation of Candida in the vagina may increase susceptibility to periodic symptomatic recurrences.

Circulating Heat Shock Proteins in Women With a History of Recurrent Vulvovaginitis

OBJECTIVE: Predisposing factors influencing recurrences of bacterial vaginosis (BV) or vaginitis from Candida remain unidentified for most women. As a component of studies to determine host susceptibility factors to genital tract infections in women, we measured expression of the 60-kDa and 70-kDa heat shock proteins (hsp60 and hsp70, respectively) in the circulation of women with or without a history of recurrent BV or candidal vaginitis and with or without a current lower genital tract infection. Heat shock protein expression is associated with a down-regulation of pro-inflammatory immune responses that would inhibit microbial infection. METHOD: The investigators measured hsp60 and hsp70, antibodies to these proteins, the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), and the anti-inflammatory cytokine interleukin-10 (IL-10) in sera by ELISA. The study population consisted of 100 women who attended a gynecology clinic in Campinas, Brazil. Of those, 55 had a history of recurrent vulvovaginitis (RV), while 45 were controls with no such history. Only women who were asymptomatic for at least 1 month were studied. RESULTS: Although all were asymptomatic, clinical and microbiological examination revealed that five of the women with a history of RV and two controls had a current candidal vaginal infection; 16 RV patients and 12 controls had BV; and six RV patients had both BV and candidiasis. Twenty-eight RV patients and 31 controls had no clinical or microbiological detectable vaginal infection. Among the RV patients, hsp60 and hsp70 were more prevalent in those with current BV (40.9% and 50.0%, respectively) or a candidal infection (45.5% and 54.5%) than in women with no current infection (21.4% and 17.9%). In the women with no history of RV, BV was not associated with a high prevalence of hsp60 (8.3%) or hsp70 (8.3%). Interleukin-10 and TNF were not more prevalent in vaginitis patients or controls with a current candidal infection or BV than in uninfected subjects. CONCLUSION: The high prevalence of circulating hsp60 and hsp70 in women with a history of RV and current BV or vaginal candidiasis, but not in women with no history of RV, suggests that differences in heat shock protein induction may be related to susceptibility to recurrent vaginal infections.

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.

Relationship between Ureaplasma urealyticum Vaginal Colonization and Polymorphism in the Interleukin-1 Receptor Antagonist Gene

The relationship between polymorphisms in the interleukin-1 receptor antagonist (IL-1ra) gene and microbial vaginal colonization was examined in 88 asymptomatic women of reproductive age. Alleles of the intron 2 region of the IL-1ra gene were identified by polymerase chain reaction (PCR). PCR was also used to detect Ureaplasma urealyticum, Mycoplasma hominis, and Candida albicans; bacterial vaginosis (BV) was identified by clinical criteria. Among the 31 women with vaginal U. urealyticum, only 3 (9.7%) were homozygous for allele 2 of the IL-1ra gene; 21 (36.8%) of the 57 women who were negative for this organism were positive for allele 2 (P=.006). Only 7 women were positive for M. hominis; none were allele 2 homozygotes as opposed to 24 (29.6%) of the 81 women negative for M. hominis. There was no relation between C. albicans or BV and any IL-1ra allele. Reduced susceptibility to vaginal colonization with mycoplasmas may be associated with homozygosity of the 2 allele of the IL-1ra gene.

Chlamydia trachomatis Infection, Immunity, and Pregnancy Outcome

Chlamydia trachomatis can ascend from the cervix to the fallopian tubes and survive for long periods of time without causing symptoms. The immune response to infection clears the extracellular organisms but leads to development of a persistent intracellular infection. Repeated cycles of productive infection and persistence eventually induce tubal occlusion and infertility. Persistently infected cells continue to synthesize the chlamydial 60 kD heat shock protein (hsp60). Immunity to conserved regions of hsp60 may result in autoimmunity to human hsp60. Expression of hsp60 by the embryo and decidua during early pregnancy may reactivate hsp60-sensitized lymphocytes, disturb pregnancy-induced immune regulatory mechanisms, and lead to immune rejection of the embryo. Due to this mechanism women with tubal infertility who are sensitized to the human hsp60 may have a decreased probability of successful outcome after undergoing in vitro fertilization and embryo transfer.

Immune sensitization to the 60 kD heat shock protein and pregnancy outcome

Heat shock proteins are highly conserved proteins present in organisms ranging from bacteria to man. They are both dominant microbial immunogens and among the first proteins produced during mammalian embryo development. Since bacterial and human heat shock proteins share a high degree of amino acid sequence homology, it has been suggested that sensitization to bacterial heat shock proteins during an infection may result in autoimmunity to human heat shock proteins. Infertile couples seeking in vitro fertilization (IVF) may have been previously sensitized to bacterial heat shock proteins as a consequence of an asymptomatic upper genital tract infection. Due to daily clinical monitoring and precisely timed fertilization these patients are an ideal study group to investigate the effect of prior sensitization to heat shock proteins on preimplantation embryo development and implantation failure. Immune sensitization at the level of the cervix to the 60 kD heat shock protein (hsp60) has been associated with implantation failure in some IVF patients. Similarly, the highest prevalence of circulating hsp60 antibodies among IVF patients was found in the sera of women whose embryos failed to develop in vitro. To more directly assess whether humoral immunity to hsp60 influenced in vitro embryo development, a mouse embryo culture model was established. Monoclonal antibody to mammalian hsp60 markedly impaired mouse embryo development in vitro. These data suggest that immune sensitization to human hsp60, possibly developed as a consequence of infection, may adversely affect pregnancy outcome in some patients.

Human papillomavirus in the vaginal introitus in women infected with the human immunodeficiency virus.

The report on Ureaplasma urealyticum in the vaginal introitus of HIV-infected women and its relation to circulating HIV RNA levels has prompted the authors to examine the same subjects for introital levels of human papillomavirus (HPV). Genital HPV infections occur with high prevalence in HIV-infected women. Paired introital and cervical specimens from 52 consecutive diagnosed and untreated HIV-seropositive women were tested using degenerate consensus primer pairs to the conserved L1 gene. Findings show that 36 (69.2%) of the cervical specimens were positive for HPV. The virus was detected in the introitus in 21 (58.4%) of the women positive for cervical HPV. HIV-1 RNA levels greater than 10000 copies/ml were identified in the circulation of 14 (26.9%) women; 9 (64.3%) of these women had HPV identified in the introitus. HIV-1 RNA levels greater than 1000 copies/ml were present in 29 (55.8%) women; 23 (79.3%) of them with introital HPV. Moreover it was suggested that HIV-infected women with HPV in the introitus might need more frequent monitoring for other infections and a possible malignancy as compared with women whose introital specimens were negative for HPV.