Immunocompetent Women Research Articles

Quadrivalent HPV (4vHPV) vaccine immunogenicity and safety in women using immunosuppressive drugs due to solid organ transplant

IntroductionImmunocompromised persons are at high risk of persistent Human Papilloma Virus (HPV) infection and associated diseases. Few studies evaluated HPV vaccines in immunocompromised persons. This study aimed to evaluate the quadrivalent HPV vaccine (4vHPV) immunogenicity and safety in solid organ transplant (SOT) recipients, in comparison to immunocompetent women (IC).MethodsOpen-label clinical trial that enrolled SOT recipients and immunocompetent women aged 18 to 45 years. All participants received three doses of 4vHPV vaccine. Blood samples were drawn for evaluation of immune responses at baseline and one month after the third vaccination. Seroconversion rates and antibody geometric mean concentration (GMC) against HPV 6, 11, 16, 18, 31, 35, 52 and 58 were measured with in-house multiplexed serology assay (xMAP technology). Follow-up for the local and systemic adverse events (AEs) continued for seven days after each vaccination. Severe AEs were evaluated throughout the study.Results125 SOT and 132 immunocompetent women were enrolled; 105 (84%) SOT and 119 (90%) immunocompetent women completed the study. At baseline, HPV seropositivity was not significantly different between groups. Seroconversion rates were significantly lower in SOT (HPV18, 57%; HPV6 and 16, 69%; and HPV11, 72%) than in immunocompetent women (100% seroconversion to all vaccine types) (p<0.001). Antibody GMCs of all four HPV vaccine types were also significantly lower in SOT (p<0.001). Pain in the injection site and headache were the most frequent adverse event in both groups. Local pain was more frequent in immunocompetent women than in SOT recipients. Rates of other AEs were comparable in both groups.Conclusion4vHPV vaccine was well-tolerated by SOT recipients. We found strong evidence of lower humoral immune responses to 4vHPV vaccine in SOT compared to immunocompetent women, which strengthen recommendation of routine cervical cancer screening in SOT recipients regardless of HPV vaccination status.

The anti-staphylococcal fusidic acid as an efflux pump inhibitor combined with fluconazole against vaginal candidiasis in mouse model

BackgroundCandida albicans is the most common fungus that causes vaginal candidiasis in immunocompetent women and catastrophic infections in immunocompromised patients. The treatment of such infections is hindered due to the increasing emergence of resistance to azoles in C. albicans. New treatment approaches are needed to combat candidiasis especially in the dwindled supply of new effective and safe antifungals. The resistance to azoles is mainly attributed to export of azoles outside the cells by means of the efflux pump that confers cross resistance to all azoles including fluconazole (FLC).ObjectivesThis study aimed to investigate the possible efflux pump inhibiting activity of fusidic acid (FA) in C. albicans resistant isolates and the potential use of Fusidic acid in combination with fluconazole to potentiate the antifungal activity of fluconazole to restore its activity in the resistant C. albicans isolates.MethodsThe resistance of C. albicans isolates was assessed by determination of minimum inhibitory concentration. The effect of Fusidic acid at sub-inhibitory concentration on efflux activity was assayed by rhodamine 6G efflux assay and intracellular accumulation. Mice model studies were conducted to evaluate the anti-efflux activity of Fusidic acid and its synergistic effects in combination with fluconazole. Impact of Fusidic acid on ergosterol biosynthesis was quantified. The synergy of fluconazole when combined with Fusidic acid was investigated by determination of minimum inhibitory concentration. The cytotoxicity of Fusidic acid was tested against erythrocytes. The effect of Fusidic acid on efflux pumps was tested at the molecular level by real-time PCR and in silico study. In vivo vulvovaginitis mice model was used to confirm the activity of the combination in treating vulvovaginal candidiasis.ResultsFusidic acid showed efflux inhibiting activity as it increased the accumulation of rhodamine 6G, a substrate for ABC-efflux transporter, and decreased its efflux in C. albicans cells. The antifungal activity of fluconazole was synergized when combined with Fusidic acid. Fusidic acid exerted only minimal cytotoxicity on human erythrocytes indicating its safety. The FA efflux inhibitory activity could be owed to its ability to interfere with efflux protein transporters as revealed by docking studies and downregulation of the efflux-encoding genes of both ABC transporters and MFS superfamily. Moreover, in vivo mice model showed that using fluconazole-fusidic acid combination by vaginal route enhanced fluconazole antifungal activity as shown by lowered fungal burden and a negligible histopathological change in vaginal tissue.ConclusionThe current findings highlight FA’s potential as a potential adjuvant to FLC in the treatment of vulvovaginal candidiasis.

Blastomycosis: An Underrecognized Climate Sensitive Fungal Pathogen Causing Pneumonia in 52-year-old Immunocompetent Women from Southwestern Ohio—A Case Report and Literature Review

Blastomycosis, formerly known as Gilchrist disease, Chicago disease, North American blastomycosis, or Namekagos fever, is an uncommon but underappreciated fungal infection seen mostly in immunocompetent people, caused by the fungi Blastomyces. Blastomyces dermatitidis and Blastomyces gilchristii are the most common species responsible for most infections in the United States of America. Blastomycosis can cause a wide variety of diseases, the most common being pneumonia as the lungs are usually the main primary entrance source of infection after inhalation of Blastomyces spores. However, dissemination from the lungs to other organs such as skin, bones, genitourinary, and central nervous system can occur. We describe a 52-year-old female who was admitted to the hospital for unresolved pneumonia after failure to respond to multiple outpatient antibiotic treatments for a presumed diagnosis of community-acquired pneumonia, presenting with right-sided chest pain, fever, cough and weight loss for three weeks duration. Her initial Chest-X ray and CT chest revealed right middle lobe infiltrate, while her laboratory studies were significant for elevated white blood cells (WBC). The patient underwent diagnostic bronchoscopy which showed erythema of the right middle lobe bronchus with purulent secretion. Furthermore, cytology examination of specimens from bronchoalveolar lavage and bronchial brush from right middle lobe with (PAP) satin on thin prep and H&E stain on the cell block revealed an abundance of broad-base budding yeast consistent with Blastomyces organism, which was confirmed by molecular testing with DNA probe assay. Her serum and urine Blastomyces antigens were positive, above the limit of quantification. The patient was started on antifungal therapy with Amphotericin-B intravenously. In the process, her fever resolved and her respiratory symptoms slowly improved. She was discharged home with oral itraconazole which was to be continued for 6-12 months as an outpatient.

Prevalence of high-grade anal intraepithelial neoplasia in immunocompetent women treated for high-grade cervical intraepithelial neoplasia

BackgroundThe aim of the study was to evaluate the prevalence of high-grade anal intraepithelial neoplasia (AIN2-3) among immunocompetent women treated for high-grade cervical intraepithelial neoplasia (CIN2-3). Such knowledge is strongly needed to establish whether a screening program should be recommended in this group of patients. MethodsThis prospective study included a cohort of consecutive women with no known causes of immunosuppression treated with LEEP (loop electrosurgical excision procedure) for a histopathological diagnosis of CIN2-3 in our center between 2019 and 2021. Following the procedure, all patients were invited to undergo anal cytology and anal high-risk HPV-DNA testing (aHPV-DNA). In cases in which one or both tests resulted positive, a high-resolution anoscopy with a biopsy of suspicious lesions was performed. All women also completed a questionnaire on sexual habits. ResultsAt total of 100 women were enrolled in the study. Among these, eight patients had a concomitant or past diagnosis of anogenital warts, while one patient had received a previous diagnosis of high-grade vaginal intraepithelial neoplasia. Anal Pap smears were positive for low-grade lesions in three patients, while 73 women tested positive for aHPV-DNA. Histological examinations revealed the presence of AIN2-3 lesions in four patients (6.5%; 95% C.I., 1.8 to 15.7%), who subsequently underwent excisional treatment. ConclusionsWomen with a history of high-grade cervical intraepithelial neoplasia have an intermediate risk of developing high-grade anal intraepithelial neoplasia. Future studies are needed in order to assess an ideal screening approach for this condition.

Which trial do we need? Three-day course of antibiotics for acute pyelonephritis in immunocompetent women

Which trial do we need? Three-day course of antibiotics for acute pyelonephritis in immunocompetent women

The first case of Janibacter bacteremia in pregnancy: A case report and review

Clinical infection with Janibacter species is an infrequently reported event. There are a small number of cases of patients with Janibacter bacteremia recognized to date. We report the first case of Janibacter bacteremia in a pregnant woman. The bacteremia was associated with pneumonia. Such cases can be difficult to manage due to the lack of antibiotic susceptibility data for these bacteria. We also report susceptibility data for the Janibacter hoylei that was isolated in our patient. This case demonstrates that J. hoylei can be a pathogen in otherwise immunocompetent pregnant women.

Natural History of Anal HPV Infection in Women Treated for Cervical Intraepithelial Neoplasia.

Women with high-grade squamous intraepithelial lesions/cervical intraepithelial neoplasia (HSIL/CIN) are at high risk of anal human papillomavirus HPV infection, and it has also been suggested that self-inoculation of the virus from the anal canal to the cervix could explain HPV recurrence in the cervix after treatment of HSIL/CIN. We aimed to evaluate the bidirectional interactions of HPV infection between these two anatomical sites. We evaluated 68 immunocompetent women undergoing excisional treatment for HSIL/CIN. Immediately before treatment, samples from the anus and the cervix were obtained (baseline anal and cervical HPV status). Cervical HPV clearance after treatment was defined as treatment success. The first follow-up control was scheduled 4-6 months after treatment for cervical and anal samples. High resolution anoscopy (HRA) was performed on patients with persistent anal HPV infections or abnormal anal cytology in the first control. Baseline anal HPV was positive in 42/68 (61.8%) of the women. Anal HPV infection persisted after treatment in 29/68 (42.6%) of the women. One-third of these women (10/29; 34.5%) had HSIL/anal intraepithelial neoplasia (AIN). Among women achieving treatment success, cervical HPV in the first control was positive in 34.6% and 17.6% of the patients with positive and negative baseline anal HPV infection, respectively (p = 0.306). In conclusion, patients with persisting anal HPV after HSIL/CIN treatment are at high risk of HSIL/AIN, suggesting that these women would benefit from anal exploration. The study also suggests that women with anal HPV infection treated for HSIL/CIN might be at higher risk of recurrent cervical HPV even after successful treatment.

The antigen processing-associated transporter gene polymorphism: Role on gene and protein expression in HPV-infected pre-cancerous cervical lesion.

Human papillomavirus (HPV) is the major pathogen for cervical lesions. The evasion mechanism of the immune response and persistence of HPV infection can be influenced by polymorphisms (SNPs) in genes associated with transporter associated with antigen processing (TAP), which may change the peptide binding affinity or the TAP expression impacting the efficiency of peptide transport in the secretory pathway, and the presentation of peptides to cytotoxic T lymphocytes. This study aimed to evaluate the role of the TAP1 and TAP2 polymorphisms, TAP1, and TAP2 genes expressions, and protein levels in cervical cells presenting different degrees of pre-cancerous lesions in 296 immunocompetent women infected or not by HPV. TAP SNPs were genotyped by Sanger sequencing, and gene expression by real-time PCR. Aneuploidy was determined by DNA index using flow cytometry. TAP-1 and TAP-2 tissue expressions were evaluated by immunohistochemistry. The Asp697Gly SNP of TAP1 presented a risk for cellular aneuploidy (P=0.0244). HPV+ women had higher TAP-2 mRNA (P=0.0212) and protein (P<0.0001) levels. The TAP2D and TAP2E haplotypes were associated with the risk for aneuploidy and pre-cancerous lesions. In conclusion, nucleotide variability at the peptide binding region of peptide transporter genes, particularly of the TAP2 gene, may influence the HPV-peptide transportation from the cytosol to the endoplasmic reticulum, increasing the susceptibility to the development of high-grade cervical lesions.

Cytomegalovirus Specific Serological and Molecular Markers in a Series of Pregnant Women With Cytomegalovirus Non Primary Infection.

(1) Background: In a period where systematic screening of CMV during pregnancy is still debated, diagnosis of non primary infection (NPI) remains challenging and an obstacle to systematic screening. Our aim is to report kinetics of serological and molecular CMV markers of NPI. (2) Methods: We identified immunocompetent pregnant women with CMV NPI as women known to be seropositive for CMV before pregnancy who gave birth to cCMV infected infants. We performed CMV-IgG, CMV-IgM, CMV-IgG avidity and CMV PCR retrospectively on sequential serum samples collected during pregnancy. (3) Results: We collected 195 serum samples from 53 pregnant women with NPI during pregnancy. For 29/53 (55%) patients, no markers of active infection were observed (stable IgG titers, negative IgM and negative PCR). CMV PCR was positive in at least one serum for 18/53 (34%) patients and median viral load was 46 copies/mL, IQR (21-65). (4) Conclusions: For more than half of patients with confirmed CMV NPI during pregnancy, available diagnostic tools are liable to fail in detecting an active infection. These should therefore not be used and universal neonatal screening for CMV remains the only way to detect all cCMV infections.

Pregnancy-Related Tuberculous Meningitis and Immune Reconstitution Inflammatory Syndrome: A Case Series and Systematic Review.

BackgroundTuberculosis is a leading cause of death among women of reproductive age. However, tuberculous meningitis, the most severe form of extrapulmonary tuberculosis, is rarely discussed in pregnancy despite this being a unique period of immune modulation that may predispose women to active disease.MethodsWe identified and described cases of tuberculous meningitis among pregnant or postpartum women screened during meningitis clinical trials in Uganda from 2018 to 2022. We conducted a systematic literature review via PubMed/Medline and Embase for all English-language publications from 1970 to 10 July 2022, to identify additional cases.ResultsWe identified 8 cases of pregnancy-related tuberculous meningitis in Ugandan women living with human immunodeficiency virus (HIV) and 40 additional cases via systematic literature review (none HIV-positive). Of all combined cases, 50% (24/48) were diagnosed postpartum; 50% (24/48) had initial onset during pregnancy, of which 38% (9/24) had worsening of symptoms or disease relapse following pregnancy cessation. Diagnosis was missed or delayed in 33% (16/48) of cases. For those with known outcomes, maternal mortality was 23% (11/48) and fetal/neonatal mortality was 30% (13/44). Of maternal survivors, 30% (11/37) had residual neurologic deficits.ConclusionsThe true incidence of tuberculous meningitis in pregnancy or the postpartum period is unclear but likely underappreciated. To date, nearly all published cases have occurred in HIV-negative or otherwise immunocompetent women. Given the well-described physiological immunosuppression during pregnancy and subsequent reconstitution postpartum, physicians must be aware of tuberculous meningitis and pregnancy-related immune reconstitution inflammatory syndrome, especially in countries with a high burden of tuberculosis and in women living with HIV.

Dynamic Immune Profile in French Toxoplasmosis Patients.

Toxoplasma gondii infection is usually benign in Europe due to the strong predominance of type II strains. Few studies have been conducted to examine the immunological course of infection in humans and have yielded conflicting results, maybe influenced by heterogeneous parasite strains. We measured 23 immune mediators in 39, 40, and 29 sera of French noninfected, acutely infected, and chronically infected immunocompetent pregnant women, respectively. Four different cytokine patterns were identified regarding their dynamics through infection phases. For 11 of the cytokines (IFN-β, IFN-γ, IL-4, IL5, IL-6, IL-10, IL-12, IL-15, CXCL9, CCL2, and CSF2) the serum levels were significantly elevated during acute infection. The inflammatory mediators IL-1β, IL-17A, IL-18, TNF-α, and CSF3 remained unchanged during acute infection, while they were significantly lower in chronically infected compared to noninfected patients. As for the anti-inflammatory cytokines TGF-β and CCL5, their levels remained significantly elevated during chronic infection. We also observed a significant negative correlation of several cytokine concentrations with IgG levels, indicating a rapid decline of serum concentrations during the acute phase. These results indicate an anti-inflammatory pattern in chronically infected patients in a type II dominated setting and demonstrate the highly dynamic immune situation during acute infection.

A retrospective study on two cohorts of immunocompetent women treated with nonavalent HPV vaccine vs. Ellagic acid complex: outcome of the evolution of persistent cervical HPV infection.

The nonavalent HPV vaccine has demonstrated its efficacy in women and men who already suffer from HPV genital lesions, with little chances to clear the infection. The efficacy of new therapeutic or complementary alternatives as Ellagic acid plus Annona Muricata (Ellagic acid complex) has emerged recently. Our retrospective study compares the evolution of persistent cervical HPV infection in two cohorts of immunocompetent women after the administration of nonavalent vaccine or Ellagic acid complex. At Tor Vergata University Hospital, Rome, forty women in childbearing age, suffering from persistent cervical HPV infection, were enrolled in two study's groups: nonavalent HPV vaccine (20 women) vs. Ellagic acid complex tablets (20 who refused the vaccine). Cytological features, HPV DNA genotypes and mRNA oncogenic genes E6/E7 presence and clearance were analyzed and confronted between the groups. Demographics and clinical features of the cohorts were comparable. Evaluation of Pap smear, HPV DNA test and mRNA genes E6/E7, were performed at baseline (T0) and after 6 months (T1) and 12 months (T2) from the last dose of vaccine/tablet. At T1 and T2, Ellagic acid complex group showed a statistical reduction of abnormalities in Pap smears (p = 0.018 and 0.006, respectively), probably due to its direct anti-inflammatory, antioxidative and antiviral activities. At T1, vaccinated group showed a higher rate of HPV clearance (p = 0.001), instead Ellagic acid complex group didn't report significative differences. At T2, respect to T0, both groups showed an increase in percentage of negative HPV DNA detection, although more marked for vaccinated group respect to Ellagic acid complex group (p = 0.039 and 0.062 respectively). Regarding mRNA E6/E7 clearance, at T1 and T2, the group of vaccinated women showed a higher negativization respect to the other group (p= 0.077 and 0.042, respectively). Despite the limited sample of women enrolled for the present study, the results confirmed the clinical usefulness of HPV vaccination as adjuvant agent for the immune system of women affected by persistent HPV infection. Moreover, in women who refused to be vaccinated, the administration of a biocompound like Ellagic acid plus Annona Muricata, represented an interesting clinical strategy in terms of increasing chance of HPV viral clearance.

Cytomegalovirus infection in immunocompetent pregnant women: clinical manifestations and management tactics

Objective: to analyze clinical manifestations, diagnostic and therapeutic approaches to management of pregnant women with cytomegalovirus infection for optimization of clinical and laboratory diagnostics and reduction of risks of congenital cytomegalovirus infection in the postnatal period.Materials and methods: in the article describe results a retrospective study the pregnancy course of 92 women who had 94 children with a confirmed congenital manifest form of cytomegalovirus infection. The inclusion criteria in main group were women aged 18-40 years and presence the results of examination for TORCH-syndrome in the first trimester of pregnancy, negative results for HIV. Markers of cytomegalovirus infection were determined by PCR (blood, vaginal secretions) and serologically (IgM, IgG to CMV-infection).Findings: the study showed that acute cytomegalovirus infection was documented during pregnancy in 18.4% of cases, and recrudescence of CMV-infection only in 33.6% of cases. Acute cytomegalovirus infection was asymptomatic in 35.3% of patients, the rest had nonspecific symptoms in the form of fatigue and headache, cholestasis was registered in 35.2% of cases, whereas with recrudescence of cytomegalovirus infection, catarrhal symptoms in the form of rhinitis and pharyngitis prevailed 42,8% cases, p&lt;0,05. 15 people received therapy during pregnancy: 2 of them – antiviral (valgancyclovir), 11 – immunocorrective (interferon2alfa) and 2 – pathogenetic therapy (blood transfusion to the fetus for anemia). Based on the literature data and obtained by analyzing management tactics of the observed pregnant women, an algorithm for the management of pregnant women with cytomegalovirus infection was created.Conclusion: the study made it possible to substantiate algorithm of diagnosis and tactics management of cytomegalovirus infection in immunocompetent pregnant women and gave recommendations for obstetricians and gynecologists about alertness regarding cytomegalovirus infection.

Cytology-based Screening for Anal Intraepithelial Neoplasia in Immunocompetent Brazilian Women with a History of High-Grade Cervical Intraepithelial Neoplasia or Cancer.

To determine the prevalence and possible variables associated with anal intraepithelial neoplasia and anal cancer in immunocompetent women with high-grade cervical intraepithelial neoplasia. A cross-sectional study involving immunocompetent women with a histological diagnosis of high-grade cervical intraepithelial neoplasia and cervical cancer, conducted between January 2016 and September 2020. All women underwent anal cytology and answered a questionnaire on characterization and potential risk factors. Women with altered cytology were submitted to anoscopy and biopsy. A total of 69 women were included in the study. Of these, 7 (10.1%) had abnormal anal cytology results: (high-grade lesion, atypical squamous cells of undetermined significance, and atypical squamous cells, cannot exclude high-grade lesions: 28,5% each; low grade lesion: 14,3%). Of the anoscopies, 3 (42.8%) showed alterations. Of the 2 (28,5% of all abnormal cytology results) biopsies performed, only 1 showed low-grade anal intraepithelial neoplasia. The average number of pregnancies, vaginal deliveries, and abortions was associated with abnormal anal cytology. However, the highest mean regarding the cesarean sections was associated with normal cytology. The prevalence of anal intraepithelial neoplasia was compatible with data from recent studies, especially those conducted in Brazil. Opportunistic screening for anal intraepithelial neoplasia in this high-risk population should be considered. Anal cytology is suitable for this purpose, due to its low cost and feasibility in public health services.

Different human papillomavirus types share early natural history transitions in immunocompetent women.

Necessary stages of cervical carcinogenesis include acquisition of a carcinogenic human papillomavirus (HPV) type, persistence associated with the development of precancerous lesions, and invasion. Using prospective data from immunocompetent women in the Guanacaste HPV Natural History Study (NHS), the ASCUS-LSIL Triage Study (ALTS) and the Costa Rica HPV Vaccine Trial (CVT), we compared the early natural history of HPV types to inform transition probabilities for health decision models. We excluded women with evidence of high-grade cervical abnormalities at any point during follow-up and restricted the analysis to incident infections in all women and prevalent infections in young women (aged <30 years). We used survival approaches accounting for interval-censoring to estimate the time to clearance distribution for 20 529 HPV infections (64% were incident and 51% were carcinogenic). Time to clearance was similar across HPV types and risk classes (HPV16, HPV18/45, HPV31/33/35/52/58, HPV 39/51/56/59 and noncarcinogenic HPV types); and by age group (18-29, 30-44 and 45-54 years), among carcinogenic and noncarcinogenic infections. Similar time to clearance across HPV types suggests that relative prevalence can predict relative incidence. We confirmed that there was a uniform linear association between incident and prevalent infections for all HPV types within each study cohort. In the absence of progression to precancer, we observed similar time to clearance for incident infections across HPV types and risk classes. A singular clearance function for incident HPV infections has important implications for the refinement of microsimulation models used to evaluate the cost-effectiveness of novel prevention technologies.

Cervicovaginal loads of Gardnerella spp. are increased in immunocompetent women with persistent high-risk human papillomavirus infection.

Introduction. Two high-oncogenic-risk human papilomavirus (hrHPV) genotypes - HPV16 and HPV18 - cause most of the cases of cervical cancer worldwide. Bacterial vaginosis is associated with increased hrHPV persistence, although the mechanism underlying this association remains unclear. Gardnerella spp. are detected in nearly all cases of bacterial vaginosis and are the major source of cervicovaginal sialidases. The NanH1 gene is present in virtually all Gardnerella sialidase-producing strains and has been proposed as a potential marker for persistent hrHPV infection.Hypothesis. Gardnerella spp. load and the NanH1 gene are associated with hrHPV persistence.Aim. To compare the cervicovaginal load of Gardnerella spp. and the frequency of the NanH1 gene between women with persistent HPV16 and/or HPV18 infection and those who cleared the infection after 11 months.Methodology. Among a population of 1638 HPV screened, we detected 104 with positive HPV16 and/or HPV18 results. Samples were obtained at two time points (baseline and at a median of 11 months at follow-up) and tested using the Linear Array HPV Genotyping kit (Roche Molecular Systems, Pleasanton, CA, USA). Based on their HPV16/HPV18 status at enrolment and follow-up, participants were assigned to 'persistence' or 'clearance' groups. We used cervicovaginal fluid samples obtained upon enrolment to determine the load of the 23 s rRNA gene of Gardnerella spp. and the presence of the NanH1 gene using real-time polymerase chain reaction (PCR). We compared Gardnerella spp. loads and NanH1 frequency between the groups by, respectively, Mann-Whitney and chi-squared tests, with a P-value <0.05 considered to be significant.Results. Of the 104 participants who were positive for HPV16/HPV18, 73 (70.2 %) persisted with at least 1 of the baseline genotypes at follow-up, while 31 (29.8 %) cleared the infection in this time frame. Participants in the persistence group had significantly higher loads of Gardnerella spp. [5.8E+02 (0-3.0E+05) copies µl-1] than those in the clearance group [9.9E+01 (0-7.7E+04) copies µl-1] (P=0.03). The baseline frequency of NanH1 was higher in the persistence' (n=46, 63.0 %) than in the clearance (n=14, 45.2 %) group, although this was not statistically significant (P=0.09).Conclusion. These findings reinforce the negative effect of vaginal microbiota for the clearance of hrHPV and indicate a possible association between sialidase-producing species with hrHPV persistence.

Anal High-risk HPV and Liquid-based Cytology of Immunocompetent Brazilian Women with Genital High-risk HPV.

The purpose of this study was to compare the frequency of the occurrence of high-risk human papillomavirus (HPV) and abnormal anal cytology in immunocompetent women with and without HPV-induced genital lesions. This analytical cross-sectional, observational study was conducted between July 2017 and December 2018 in a specialized outpatient clinic of a tertiary hospital in Fortaleza, CE. Fifty-seven immunocompetent women with and without genital intraepithelial lesions were assessed; they were divided into two groups: group 1 was comprised of women with HPV-associated genital lesions (n = 26), and group 2 was comprised of those without HPV-associated genital lesions (n = 31). Samples for liquid-based cytology and high-risk DNA-HPV polymerase chain reaction real-time tests were collected from the cervix and anus. All cases were evaluated using high-resolution anoscopy; biopsies were performed when required. The Fisher exact and chi-squared tests were applied for consolidated data in the contingency table, and the Student t-test and Mann-Whitney U-test for independent variables. Anal high-risk HPV infections were more frequent in group 1 (odds ratio [OR], 4.95; 95% confidence interval [CI], 1.34-18.3; p = 0.012), along with concomitant high-risk HPV infections in the uterine cervix and the anus (OR 18.8; 95% CI, 2.20-160; p < 0.001). The incidence of high-risk cervical HPV infection was associated with high-risk anal HPV infection (OR, 4.95; 95% CI, 1.34-18.3; p = 0.012). There was no statistical difference concerning abnormal anal cytology or anoscopy between the groups, and no anal intraepithelial lesion was found in either group. Immunocompetent women with HPV-associated genital lesions and high-risk cervical HPV were more likely to have high-risk anal HPV.

Human Papillomavirus (HPV) seroprevalence, cervical HPV prevalence, genotype distribution and cytological lesions in solid organ transplant recipients and immunocompetent women in Sao Paulo, Brazil

IntroductionSolid organ transplant (SOT) recipients are at increased risk of Human Papillomavirus (HPV) persistent infection and disease. This study aimed to evaluate HPV seroprevalence, cervical HPV prevalence, genotype distribution, and frequency of HPV-related cervical lesions in SOT recipients in comparison to immunocompetent women.MethodsCross-sectional study including SOT and immunocompetent women aged 18 to 45 years who denied previous HPV-related lesions. Cervical samples were screened for HPV-DNA by a polymerase chain reaction (PCR)-based DNA microarray system (PapilloCheck®) and squamous intraepithelial lesions (SIL) by liquid-based cytology. A multiplexed pseudovirion-based serology assay (PsV-Luminex) was used to measure HPV serum antibodies.Results125 SOT and 132 immunocompetent women were enrolled. Cervical samples were collected from 113 SOT and 127 immunocompetent women who had initiated sexual activity. HPV-DNA prevalence was higher in SOT than in immunocompetent women (29.6% vs. 20.2%, p = 0.112), but this difference was not statistically significant. High-risk (HR)-HPV was significantly more frequent in SOT than in immunocompetent women (19.4% vs. 7.9%, p = 0.014). Simultaneous infection with ≥2 HR-HPV types was found in 3.1% of SOT and 0.9% of immunocompetent women. HPV seropositivity for at least one HPV type was high in both groups: 63.8% of 105 SOT and 69.7% of 119 immunocompetent women (p = 0.524). Low-grade (LSIL) and high-grade SIL (HSIL) were significantly more frequent in SOT (9.7% and 5.3%, respectively) than in immunocompetent women (1.6% and 0.8%, respectively) (p = 0.001).ConclusionsThese results may reflect the increased risk of HPV persistent infection and disease progression in SOT women due to chronic immunosuppression.

Recurrent stroke in varicella zoster associated vasculopathy

Varicella zoster virus (VZV) is well known for its neurotropism, primary infection and reactivation after variable latency periods. After reactivation from spinal or cranial nerve ganglia, viruses can affect the central nervous system and cranial vasculature via transaxonal migration followed by transmural spread from the adventitial layer to the intima. Stroke can occur following primary infection by VZV (varicella) or after reactivation (zoster). These infectious vasculitides by VZV can lead to unifocal or multifocal ischemic and hemorrhagic stroke either after cranial nerve or spinal dermatomal zoster. Usual difference between immunocompetent versus immunocompromised individuals is involvement of unifocal large vessel vasculopathy in the former while multifocal small vessel in later. This vasculopathy in some cases may be progressive leading to recurrent stroke even after antiviral treatment. Diagnosis becomes challenging and needs a high degree of suspicion in immunocompetent, younger individuals, in absence of rash and when there are comorbidities. We report a case of elderly immunocompetent women, who developed multifocal infarcts followed by ventricular and subarachnoid haemorrhage after thoracic varicella zoster. Diagnosis was confirmed by the presence of anti-VZV IgG antibodies in the cerebrospinal fluid. In view of the diverse clinic-radiological spectrum of VZV vasculopathy, early recognition of this clinical entity is warranted for improved outcome.

Toxoplasma gondii in South America: a differentiated pattern of spread, population structure and clinical manifestations.

Toxoplasma gondiiis an obligate intracellular parasite belonging to the phylum Apicomplexa. It has a worldwide distribution and can infect a wide variety of intermediate hosts, including humans. In South America, toxoplasmosis shows high health impacts, and the incidence of the disease is frequently reported and more severe than in other regions, such as Europe. Although most T. gondii infections are asymptomatic, severe manifestations can occur in cases of congenital toxoplasmosis and immunocompromised individuals. In South America, the ocular disease in immunocompetent individuals is also frequently reported. Treatment for any clinical manifestation of toxoplasmosis consists of the combination of sulfadiazine (SDZ) and pyrimethamine (PYR). However, failures in the treatment of toxoplasmosis have been reported, especially in South America, suggesting the acquisition of resistance against SDZ and PYR. Another paradigm present in the literature is that once infected withT. gondii, the host is immunologically protected from further reinfections. However, some studies indicate cases of congenital transmission ofT. gondiifrom immunocompetent pregnant women with chronic infection, suggesting the possibility of reinfection in humans. Thus, in this review, we will cover several aspects of South AmericanT. gondiiisolates, such as genetic characterization, disease manifestation, host reinfection and drug resistance.