Paulo César Giraldo

Contemporary perspectives on vaginal pH and lactobacilli

Ever since the pH of the vagina was found to be much more acidic than blood and interstitial fluids, a belief going back more than a century has persisted that the vagina is protected from pathogenic organisms by the high level of hydronium ions present. A corollary of this belief is that the pH of the vagina and antipathogen activity is due to colonizing Lactobacilli. Unfortunately, this dogma lacks empirical research support. The vaginal pH is determined by the interplay between vaginal physiological processes and microbiology. An acidic vaginal pH and Lactobacilli are components of multiple defense mechanisms active in protection against infection in the lower female genital tract.

Mannose-binding lectin gene polymorphism, vulvovaginal candidiasis, and bacterial vaginosis.

OBJECTIVE: To evaluate associations between polymorphisms in the gene coding for mannose-binding lectin (MBL) and the diagnosis of acute or recurrent vulvovaginal candidiasis and bacterial vaginosis METHODS: Women at two outpatient clinics in Brazil filled out a questionnaire and were examined for the presence of vulvovaginal candidiasis or bacterial vaginosis. A buccal swab was blindly tested for codons 54 and 57 MBL2 gene polymorphisms by polymerase chain reaction and endonuclease digestion. RESULTS: A total of 177 women were enrolled. Vulvovaginal candidiasis was identified in 78 (44.1%) women, 33 (18.6%) had bacterial vaginosis, and 66 (37.3%) were normal controls. Recurrent vulvovaginal candidiasis was present in 50 (64.1%) of the women with vulvovaginal candidiasis; 20 (60.6%) of the bacterial vaginosis patients had recurrent disease. Vulvovaginal candidiasis was associated with white race (P=.007), bacterial vaginosis was associated with nonwhite race (P=.05), and both were associated with a history of allergy (P≤.02) and having sexual intercourse at least three times a week (P<.001). Carriage of the variant MBL2 codon 54 allele B was more frequent in women with recurrent vulvovaginal candidiasis (25.0%) than in the women with acute vulvovaginal candidiasis (17.9%) or controls (10.6%) (P=.004). Allele B was also more prevalent in women with recurrent bacterial vaginosis (22.5%) than in those with acute bacterial vaginosis (0%) (P=.009). The MBL2 codon 57 polymorphism was infrequent and not associated with vulvovaginal candidiasis or bacterial vaginosis. CONCLUSION: The incidence of vulvovaginal candidiasis and bacterial vaginosis differs by ethnicity in Brazilian women. The MBL2 codon 54 gene polymorphism is associated with both recurrent vulvovaginal candidiasis and recurrent bacterial vaginosis. LEVEL OF EVIDENCE: III

Prevalence of cervicovaginal infections during gestation and accuracy of clinical diagnosis.

OBJECTIVES: The aim of this study was to establish the prevalence of cervicovaginal infections in normal third-trimester pregnant women and evaluate the accuracy of clinical diagnosis. METHOD: A total of 328 pregnant women were followed at the Prenatal Outpatient Clinic of the Department of Obstetrics and Gynecology at the School of Medical Sciences, Universidade Estadual de Campinas (UNICAMP), Brazil, from October 1991 to February 1993. The clinical diagnosis was based on the characteristics of the vaginal discharge, and the etiological diagnosis was based on bacterioscopy of the vaginal secretion and direct immunofluorescence for Chlamydia trachomatis. The data were analyzed statistically, determining the sensitivity, specificity, and positive and negative predictive value of the clinical diagnosis related to the laboratory diagnosis of the different infections. RESULTS: The prevalence of infection was 39.6% (Candida albicans, 19.2%; bacterial vaginosis, 9.5%; intermediate vaginal flora, 6.7%; Chlamydia trachomatis, 2.1%; and vaginal trichomoniasis, 2.1%). The accuracy of clinical diagnosis was low, with sensitivity between 50% and 65% and specificity around 60%, with the exception of trichomoniasis, which showed a sensitivity of 100% and chlamydia, with a sensitivity of 0% and a specificity of 100%. CONCLUSION: The accuracy of the clinical diagnosis of infections was low, specifically with respect to the positive predictive value. The results demonstrate the need for specific testing of cervicovaginal infections at prenatal visits. Reliance on simple vaginal examination results in a low yield for detection of vaginal infections.

An Altered Immunity Hypothesis for the Development of Symptomatic Bacterial Vaginosis

The hypothesis is advanced that the transition from a Lactobacillus-dominated vaginal microflora to a microflora characteristic of bacterial vaginosis (BV), as well as development of the adverse consequences of BV in some women but not in others, are due to alterations in innate immunity. A microbial-induced inhibition of Toll-like receptor expression and/or activity may block induction of proinflammatory immunity and lead to the proliferation of atypical vaginal bacteria. A lack of 70-kDa heat-shock protein production and release in response to abnormal flora would compound this failure to activate antimicrobial immune responses. A deficit in vaginal mannose-binding lectin concentrations would further decrease the capacity for microbial killing and increase the likelihood of bacterial migration from the vagina to the upper genital tract.

Evaluation of the secretory immunoglobulin A levels in the colostrum and milk of mothers of term and pre-trerm newborns

OBJECTIVE To determine and to compare the levels of secretory immunoglobulin A in samples of colostrum and milk of mothers of term and preterm neonates. MATERIAL AND METHODS The levels of secretory immunoglobulin A of 10 mothers of term neonates and 10 mothers of preterm neonates were determined from 5 mL of colostrum or milk collected on the 1st, 4th, 10th and 15th days of the puerperal period, using the radial immunodiffusion technique. We employed anamnesis, as well as physical and gynecological exams in women in the puerperal period. All the patients were attended at the Januário Cicco Maternity College. RESULTS The secretory immunoglobulin A levels were significantly higher in the colostrum and milk of mothers of preterm neonates when compared with the levels found in colostrum and milk of mothers of term neonates (Mann-Whitney test, p<0.0001). There was a significant decline in the secretory immunoglobulin A levels of the colostrum and milk of the mothers of term and preterm neonates during the four periods (Kruskal-Wallis test, p<00001). CONCLUSIONS The secretory immunoglobulin A levels in colostrum and milk of mothers of preterm neonates were significantly higher than in the mothers of term neonates, demonstrating immunological adaptation in preterm neonate breast-feeding.

Effects of physical activity on breast cancer prevention: a systematic review.

BACKGROUND Observational studies have reported an association between physical activity and breast cancer risk reduction. This study aims to evaluate the effect of physical activity on breast cancer prevention. METHODS Articles were identified through literature available on Electronic databases (PubMed, Embase, Scielo, Cochrane, CINAHL, Cancerlit, and Google Scholar) and manual searches. Case control and cohort studies were assessed for methodological quality, using the Newcastle-Ottawa scale. RESULTS Size, population, components, and characteristics of physical activity, and menopausal status were documented. Review Manager 5.1 performed analysis using the statistical method of Mantel-Haenszel. Fixed-effect analysis with dichotomous data, testing subgroups and calculating odds ratio with a confidence interval of 95% were used. MAIN RESULTS 7 cohort studies and 14 case control studies were evaluated. Statistical evidence found that physical activity reduces the risk of breast cancer in case-control studies [OR = 0.84 (0.81-0.88)] (heterogeneity 72%) and cohort studies [OR = 0.61 (0.59-0.63)] (heterogeneity 100%). CONCLUSION Physical activity seems to prevent breast cancer mainly in postmenopausal women.

HIV infection in women: impact on contraception.

A study was performed to evaluate the impact of knowledge of HIV infection (diagnosis) on contraception information and choices for HIV infected women. A questionnaire was given to 140 HIV infected women. Most of the studied population included young women with a low educational level. A significant increase in the knowledge of contraceptive methods was observed after diagnosis of being HIV infected. The data suggested that the women who received information had never received it before, or that the diagnosis created a stronger motivation to listen to the counseling offered. A significant increase in the use of contraceptive methods was also found, especially male condoms and tubal ligation. Total number of children had a strong impact on contraceptive method at the time of interview. Only 5 of 23 HIV infected women who had no children used hormonal contraceptives, while 15 of 23 preferred condom use, and 3 of 23 chose not to use any contraceptive method. Tubal ligation was performed in approximately 9% of the women who had only one child. However, 12.4% of the sexually active HIV infected women were still not using any contraceptive method at the time of the interview. A combined method (male condom plus another contraceptive) was used by only 27% of sexually active HIV infected women, despite health service counseling. In conclusion, the realization of being HIV infected had a strong impact on contraceptive practice among these women. It is expected that HIV and family planning clinics will address HIV infected womens needs and be prepared to integrate contraception and gynecological care.

Sexual behavior and knowledge of sexually transmitted infections among university students in Sao Paulo, Brazil

To investigate the sexual behavior and knowledge about sexually transmitted infections (STIs) among undergraduate students in Sao Paulo, Brazil.

Prognostic markers of high-grade squamous intraepithelial lesions: the role of p16INK4a and high-risk human papillomavirus.

Background. p16INK4a seems to be an indicator of the grade of Human Papillomavirus‐induced lesions and a possible predictor of the lesion evolution. There are few studies about the role of HPV test and p16INK4a in diagnosis of high‐grade cervical lesions in South‐American women. The aim of the present study was to evaluate the presence of p16INK4a and high‐risk HPV‐DNA expression in cases diagnosed as squamous intra‐epithelial lesion and evaluate their role in the approach of high‐grade squamous intra‐epithelial lesion. Methods. p16INK4a and high‐risk Human papillomavirus were investigated in 96 samples of the cervix (13 cases of high grade squamous intraepithelial lesions, 26 cases of low grade intraepithelial lesions and 57 normal tissues). The p16INK4a was identified by immunohistochemistry using the p16INK4a kit (E6H4 clone, DakoCytomation, Carpinteria, CA) and Human papillomavirus DNA was classified by hybrid capture (Digene®). Associations were evaluated by the KAPPA index. Results. The p16INK4a was detected in 92.3% of the high‐grade squamous intraepithelial lesions, in 15.4% of the low‐grade and in none of the normal tissues. The sensitivity, specificity, positive predictive value and negative predictive value for high‐grade lesion were 92.3%, 100%, 100%, and 98.3%, respectively when considering p16INK4a expression, and 100%, 70.2%, 43.3% and 100%, respectively when considering high‐risk HPV. Conclusions. p16INK4a test was better associated with high‐grade intraepithelial lesion (κ = 0.95) than was the presence of high‐risk HPV (κ = 0.47). Both tests could be complementary to high‐grade squamous intra‐epithelial lesion screening and help to define the diagnosis of the inconclusive low‐grade/high‐grade squamous intraepithelial lesion cases.

Safety, tolerability and side effects of human papillomavirus vaccines: a systematic quantitative review

Recently, many studies have evaluated HPV vaccine safety and adverse effects. Two vaccines have been recently evaluated in randomized controlled trials: the bivalent vaccine for HPV 16 and 18 (Cervarix, GlaxoSmithKline Biologicals, Rixensart, Belgium) and the quadrivalent vaccine for HPV 6, 11, 16, and 18 (Gardasil, Merck and Co., Inc., Whitehouse Station, NJ). We have performed a systematic review of all randomized controlled trials in which HPV vaccines were compared with placebo regarding safety, tolerability and adverse effects. Studies were searched up to March 2013 in the databases: Pubmed, Embase, Scielo and Cancerlit. Odds Ratios (OR) of most incident adverse effects were obtained. Twelve reports, involving 29,540 subjects, were included. In the HPV 16/18 group, the most frequently reported events related to the vaccine were pain (OR 3.29; 95% CI: 3.00-3.60), swelling (OR 3.14; 95% CI: 2.79-3.53) and redness (OR 2.41; 95% CI: 2.17-2.68). For the HPV 6/11/16/18 group the events were pain (OR 2.88; 95% CI: 2.42-3.43) and swelling (OR 2.65; 95% CI: 2.0-3.44). Concerning the HPV 16/18 vaccine, pain was the most common outcome detected. These effects can be due to a possible VLP-related inflammation process. Fatigue was the most relevant general effect observed followed by fever, gastrointestinal symptoms, and headache. In the HPV 6/11/16/18 group, only general symptoms, pain and swelling were observed. Pain and swelling were the most frequent. Comparing HPV 16/18 to HPV 6/11/16/18 vaccines, the former presented more adverse effects, perhaps because there are many more trials evaluating the bivalent vaccine. Other studies are needed to clarify this issue.