Asymptomatic Genital Infection Research Articles

IFNγ insufficiency during mouse intra-vaginal Chlamydia trachomatis infection exacerbates alternative activation in macrophages with compromised CD40 functions

Chlamydia trachomatis (C.tr), an obligate intracellular pathogen, causes asymptomatic genital infections in women and is a leading cause of preventable blindness. We have developed in vivo mouse models of acute and chronic C. trachomatis genital infection to explore the significance of macrophage-directed response in mediating immune activation/suppression. Our findings reveal that during chronic and repeated C. trachomatis infections, Th1 response is abated while Treg response is enhanced. Additionally, an increase in exhaustion (PD1, CTLA4) and anergic (Klrg3, Tim3) T cell markers is observed during chronic infection. We have also observed that M2 macrophages with low CD40 expression promote Th2 and Treg differentiation leading to sustained C. trachomatis genital infection. Macrophages infected with C. trachomatis or treated with supernatant of infected epithelial cells drive them to an M2 phenotype. C. trachomatis infection prevents the increase in CD40 expression as observed in western blots and flow cytometric analysis. Insufficient IFNγ, as observed during chronic infection, leads to incomplete clearance of bacteria and poor immune activation. C. trachomatis decapacitates IFNγ responsiveness in macrophages via hampering IFNγRI and IFNγRII expression which can be correlated with poor expression of MHC-II, CD40, iNOS and NO release even following IFNγ supplementation. M2 macrophages during C. trachomatis infection express low CD40 rendering immunosuppressive, Th2 and Treg differentiation which could not be reverted even by IFNγ supplementation. The alternative macrophages also harbour high bacterial load and are poor responders to IFNγ, thus promoting immunosuppression. In summary, C. trachomatis modulates the innate immune cells, attenuating the anti-chlamydial functions of T cells in a manner that involves decreased CD40 expression on macrophages.

Chlamydia trachomatisinfection renders M2 generation to mediated immunosuppression.

Abstract Chlamydia trachomatis (C.tr) cause asymptomatic genital infections in women and is also a leading cause of preventable blindness. Limited mouse model of chronic C.tr infection are available to study the host immune response. We have developed BALB/c mice models of acute and chronic infections for C. trachomatisto explore the significance of macrophage-directed response in mediating immune activation/suppression. We observed that chronic and repeated infections accompanied abbrogated IFN-g and promoted enhanced TGF-β and IL-10 secretion. The signs of T cell exhaustion and anergy were also indicated during chronic and secondary infection. This skewed T cell response was established to be the regulated by alternatively-activated macrophages with low CD40 expression leading to sustained C. trachomatis genital infection. Macrophages under the influence of C. trachomatis infection or its secretome demonstrate an M2-macrophage subset phenotype which responded poorly to IFN-g owing to decreased IFNg-RI and IFNg-RII expression which correlated with decreased expression/release of MHC-II, CD40, iNOS and NO even following IFN-g treatment. Alternatively-activated M2 macrophages with low CD40 expression harbored high bacterial load and rendered the generation of immunosuppressive Th2 and Treg cells. Thus, C. trachomatis modulate the innate immune cells attenuating the anti-chlamydial functions of T cells in a manner that involves alleviated CD40 expression on macrophages.

Endocrine Disorders and Genital Infections Impair Gynecological Health in APECED (APS-1).

ObjectiveIn autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) defects in the autoimmune regulator gene lead to impaired immunotolerance. We explored the effects of immunodeficiency and endocrinopathies on gynecologic health in patients with APECED.DesignCross-sectional cohort study combined with longitudinal follow-up data.MethodsWe carried out a gynecologic evaluation, pelvic ultrasound, and laboratory and microbiologic assessment in 19 women with APECED. Retrospective data were collected from previous study visits and hospital records.ResultsThe study subjects’ median age was 42.6 years (range, 16.7-65.5). Sixteen patients (84%) had premature ovarian insufficiency, diagnosed at the median age of 16.5 years; 75% of them used currently either combined contraception or hormonal replacement therapy. In 76% of women, the morphology and size of the uterus were determined normal for age, menopausal status, and current hormonal therapy. Fifteen patients (79%) had primary adrenal insufficiency; three of them used dehydroepiandrosterone substitution. All androgen concentrations were under the detection limit in 11 patients (58%). Genital infections were detected in nine patients (47%); most of them were asymptomatic. Gynecologic C. albicans infection was detected in four patients (21%); one of the strains was resistant to azoles. Five patients (26%) had human papillomavirus infection, three of which were high-risk subtypes. Cervical cell atypia was detected in one patient. No correlation between genital infections and anti-cytokine autoantibodies was found.ConclusionsOvarian and adrenal insufficiencies manifested with very low androgen levels in over half of the patients. Asymptomatic genital infections, but not cervical cell atypia, were common in female patients with APECED.

Detection of Vaginal Metabolite Changes in Premature Rupture of Membrane Patients in Third Trimester Pregnancy: a Prospective Cohort Study

Premature rupture of membranes (PROM) is usually associated with pregnant and neonatal complications. Most of the PROM cases are caused by ascending asymptomatic genital infection. In China, PROM (15.3%) is more common than spontaneous preterm labor (7.3%) and leads to more adverse pregnancy outcomes. Here, we designed a prospective cohort study to measure the metabolomics changes in vaginal swab samples and explored their potential contribution to PROM. A total of 260 differentially expressed metabolites were identified and further analyzed. In the PROM group, N-acetyl-d-galactosamine and sucrose were downregulated (P = 0.0025, P = 0.0195, respectively), both of which are the upstream metabolites of the glycolysis pathway. Furthermore, estriol 3-sulfate 16-glucuronide (P = 0.0154) and 2-methoxy-17beta-estradiol 3-glucosiduronic acid (P = 0.004), two final metabolites in steroid hormone biosynthesis, were both downregulated in the PROM group. Finally, we found two catechin metabolites (epigallocatechin-7-glucuronide, P = 0.0009; 4′-methyl-epigallocatechin-7-glucuronide, P = 0.01) as well as DL-citrulline (P = 0.0393) were also significantly downregulated in the PROM group compared with the healthy control (HC) group, which are related to important antioxidant and anti-inflammatory activities in the human body. Altogether, metabolite changes in glycolysis, steroid hormone biosynthesis, and antioxidant/anti-inflammatory pathways may contribute to (or be a consequence of) vaginal dysbiosis and PROM. Metabolite pathway analysis is a new and promising approach to further investigate the mechanism of PROM and help prevent its unfavorable pregnant outcomes at a functional level. Trial registration number: ChiCTR2000034721

Oligoarthritis associated with a “forgotten” IUD – a case report

Reactive arthritis has been defined as an aseptic inflammatory arthritis associated with a concomitant infectious disease. Usually, the symptoms develop during or soon after a symptomatic infectious disease, however, in both sexes genitourinary infections might be asymptomatic. 
 Herein, we presented a case of a 68-year old woman with oligoarthritis associated with a “forgotten” intrauterine device (IUD). The IUD was successfully removed by laparoscopy leading to a full resolution of symptoms and improvement of inflammatory markers.
 The presented case shows that asymptomatic genital infection should be considered in case of suspected infection-related arthritis without clear etiological cause, especially in women with IUD. The in-depth training of patients regarding the proper use of contraception methods as well as the regular gynaecological examinations might help to prevent further similar cases.

Levels of different cytokines in women and men with asymptomatic genital infection caused by Chlamydia.

Immune response to genital Chlamydia trachomatis infection is involved in both immunity and pathology. The cytokine profile during infection has been implicated in the disease outcome, either resolution or severe sequelae. In total, 3900 patients were analyzed for presence of genital infections caused by Chlamydia using molecular assays. Interleukins (IL) IL-10, IL-17, IL-6, IL-2 and chemokine IP-10 were estimated by ELISA in urine, cervical swabs and semen samples. Statistical analysis was performed using the T student test. A total of 47 out of 3900 samples (1.2%) were found to be positive for Chlamydia trachomatis based on the Real Time (RT) PCR results. Statistical analysis revealed that the differences between Chlamydia trachomatis positive and negative samples regarding levels of cytokines were not significant. Our results demonstrated that no significant difference in cytokine concentrations exists in Chlamydia trachomatis infected patients when compared to healthy controls. In further study, we aim to test on a greater number of positive samples a greater number of cytokines involved in the immune response to Chlamydia trachomatis infections.

First Detection of Chlamydia trachomatis 'Swedish' Variant (nvCT) in a Russian Couple with Infertility.

Background:Chronic asymptomatic chlamydial genital infection caused by the wild-type of Chlamydia trachomatis (wtCT) is the most common bacterial infection causing human infertility. The novel ‘Swedish’ variant of С.trachomatis (nvCT) which contains a 377 bp deletion in a region that is specifically targeted in some nucleic acid amplification tests may impede diagnosis.Objective: The study aimed to investigate whether nvCT may be a possible cause of infertility in a couple undergoing in vitro fertilization (IVF).Method:Clinical specimens from both genital (urethra and cervix) and extra-genital sites (pharynx, conjunctive, blood) of a couple who experienced multiple unsuccessful attempts at pregnancy by natural fertilization and IVF procedures were analyzed before and after antibiotic therapy. Both partners had neither somatic nor endocrinal abnormality nor any clinically apparent genital manifestations of Chlamydia or other STIs.Results:Before antibiotic therapy all the samples of the Female Partner (FP) contained DNA of only the nvCT. After antibiotic therapy, additionally, DNA of wtCT of genovars E and D was detected in specimens from her conjunctiva and oropharynx. All samples of the Male Partner (MP) revealed co-infection of nvCT and wtCT. Identical SNP within the variable region 4 (VD4) of the ompA gene confirmed the identity of the wtCT strains found in both partners. The FP had a positive anti-chlamydial IgG titer. The sperm characteristics of the MP, motility (immotile spermatozoa was 51.1% versus 21.6%) and vitality (46% versus 68%) declined progressively, and the MP anti-chlamydial IgG titer was negative.Conclusion:Infertility in this couple may have been caused by chronic asymptomatic and persistent nvCT-associated infection that was complicated by re-infection later with wtCT. This study illustrates the importance of including detection methods for nvCT strains in the investigation of infertility cases.

Antibiotic Therapy as Infertility Management

Today infertility is a common problem affecting as much as 15% of couples. Infertility is caused by a variety of reasons, with male reproductive system abnormalities accounting for a large percentage (approximately 35%) and the anatomical anomalies or lesions related to female reproductive organs equally responsible (also approximately 35%). Endometriosis, ovulation abnormalities, autoimmune disorders, genetic abnormalities and asymptomatic genital infections are also major causes of female and male infertility respectively. Unexplained infertility, presented in a large percentage of couples (25-30%), is usually due to undetectable microbial infections by the routine diagnostic techniques available. So far one of the most successful treatment methods available for unexplained infertility is the use of antimicrobial therapy. However, further research is required for the absolute confirmation of the benefits of the antimicrobial therapy as a means of infertility management.

Syphilis in Adolescents

Introduction: Syphilis is a sexually transmitted disease cause by Tepronema pallidum. The first cases were reported over 500 years ago, in Italy. Even though the worldwide efforts to eradicate the disease until the end of the 20th centure, the numbers of infections have increased in the last years, mostly among teenagers. In addiftion of the cronic complications that can remain if the infection is not properly treated, it subserves the HIV coinfection. The recent increase of reports shows that it is still a public health threat. The purpose of this article is to describe and discuss the increase of syphilis infection among adolescents, as well as its rick factors. Methodology: Cases reported to the Epidemiological Bulletin of the Health Department of the State of Pernambuco, between 2011 and 2015, were analyzed and compared. The range age was 10 to 49 years. Results: There was an increase in the number of reported cases of syphilis in all age groups. The highest proportional increase was found among adolescents, 6 times higher in 2015 than in 2011. There was also a prevalence in females due to asymptomatic genital infections, female recipient anatomy in the sexual act and gender inequality. The main risk factors are infrequent condom use, sexual abuse, school backwardness, the use of licit and illicit drugs, and low socioeconomic conditions. Concurrently with the outbreak of syphilis, there is a lack of benzathine penicillin, standard antimicrobial used for proper treatment. Pregnant adolescents are the second group with the highest incidence of the disease. This fact, along with the lack of penicillin, may predispose to an increase in newborns with congenital syphilis. It is important to emphasize that there can still be great underreporting. Conclusion: The number of cases has increased over the last years. Adolescents are by themselves a vulnerable group. It is essencial that the Government provide investment in universal access to education and health, campaigns to encourage the use of condoms, and the expansion of the discussion about gender equality. There is also an urgency for mobilization to expand production of benzathine penicillin.

Toll like receptor 4: an important molecule in recognition and induction of appropriate immune responses against Chlamydia infection.

Chlamydia species are obligate intracellular pathogens causing different infectious diseases particularly asymptomatic genital infections and are also responsible for a wide range of complications. Previous studies showed that there are different immune responses to Chlamydia species and their infections are limited to some cases. Moreover, Chlamydia species are able to alter immune responses through modulating the expression of some immune system related molecules including cytokines. Toll like receptors (TLRs) belonge to pathogen recognition receptors (PRRs) and play vital roles in recognition of microbes and stimulation of appropriate immune responses. Therefore, it appears that TLRs may be considered as important sensors for recognition of Chlamydia and promotion of immune responses against these bacterial infections. Accordingly, TLR4 detects several microbial PAMPs such as bacterial lipopolysacharide (LPS) and subsequently activates transcription from pro-inflammatory cytokines in both MYD88 and TRIF pathways dependent manner. The purpose of this review is to provide the recent data about the status and major roles played by TLR4 in Chlamydia species recognition and promotion of immune responses against these infections and also the relationship between TLR4 activities and pathogenesis of Chlamydia infections.

INFECÇÃO GENITAL POR CHLAMYDIA TRACHOMATIS E NEISSERIA GONORRHOEAE EM HOMENS ASSINTOMÁTICOS

Introdução: A infecção genital por Chlamydia trachomatis (CT) e Neisseria gonorrhoeae (NG) é frequente, sendo a infecção assintomática importante sobretudo no caso da CT. A disponibilidade de técnicas de amplificação de ácidos nucleicos de elevada sensibilidade e especificidade para o diagnóstico de infecção genital por estas bactérias levou à implementação do seu rastreio sistemático em Consultas de Infecções Sexualmente Transmissíveis (ISTs). Os autores pretenderam determinar a prevalência de infecção genital por CT e NG em homens assintomáticos numa Consulta de Venereologia e caracterizar a população testada.Métodos: Foi realizado um estudo retrospectivo em indivíduos do sexo masculino observados pela primeira vez na Consulta de Venereologia de um Serviço de Dermatologia em Lisboa, durante um período de 51 meses, rastreados para infecção genital assintomática por CT e NG.Resultados: Na população estudada (n = 199), a prevalência de infecção genital assintomática por CT e NG foi de 5% (10 doentes) e 0,5% (1 doente), respectivamente. Verificou-se uma maior prevalência de infecção por CT nos heterossexuais (7,7% vs 1,3%) e a idade mediana do grupo dos infectados mostrou-se inferior, embora não estatisticamente significativa.Conclusão: A prevalência de 5,5% de infecção genital assintomática em homens encontrada no nosso estudo está de acordo com dados epidemiológicos de outros estudos e apoia as actuais recomendações em rastrear estas infecções na Consulta de ISTs.

P06.13 Inflammatory cytokine biomarkers identify women with asymptomatic genital infections that increase the risk of hiv infection

Introduction Untreated sexually transmitted infections (STIs) and bacterial vaginosis (BV) cause genital inflammation and increased risk of HIV infection. WHO-recommended syndromic STI and BV management is limited as large numbers of women with asymptomatic infections go untreated. The purpose of this study was to evaluate genital cytokine profiles as a biomarker to identify women with asymptomatic, treatable infections. Methods Luminex was used to measure the concentrations of 42 cytokines in cervicovaginal lavages (CVL) from 227 HIV-uninfected women from Durban, South Africa, and nine cytokines in endocervical swabs from 264 women from Bondo, Kenya and Pretoria, South Africa. Women were screened for BV and treatable STIs ( Chlamydia trachomatis , Neisseria gonorrhoeae , Trichomonas vaginalis , Mycoplasma genitalium ) using microscopy and molecular assays. Nonparametric receiver operating characteristic curves and logistic regression were used to identify cytokine profiles associated with STIs/BV. Results In women from Durban, concomitant increased IL-1α and IL-1β and decreased IP-10 concentrations in CVLs predicted the presence of a treatable genital condition, correctly classifying 76% of women (sensitivity 72%, specificity 81%, PPV 86% and NPV 64%). In a separate validation cohort of women from Bondo and Pretoria, IL-1α, IL-1β and IP-10 concentrations in endocervical swabs correctly classified 72% of the participants according to STI/BV status. This approach performed substantially better than clinical signs in both cohorts from Durban (sensitivity 19%, specificity 92%, PPV 79% and NPV 40%) and Pretoria and Bondo (sensitivity 29%, specificity 78%, PPV 68%, NPV 39%). Conclusion Across two cohorts of women residing in different regions in sub-Saharan Africa, genital IL-1α, IL-1β and IP-10 together was the best immunological predictor of the presence of an STI or BV. Supplementing syndromic management with point-of-care assessment of biomarkers of genital inflammation may improve STI/BV management for women, enabling more effective treatment of asymptomatic infections and potentially reducing their risk of HIV infection. Disclosure of interest statement This work was supported by a Strategic Health Innovation Partnerships (SHIP) grant from the South African Medical Research Council and grants from the Poliomyelitis Research Foundation (PRF) of South Africa and European and Developing Countries Clinical Trials Partnership (EDCTP). The cohorts were supported by grants from the Comprehensive International Program of Research on AIDS (CIPRA) of the Division of AIDS (DAIDS); National Institute of Allergy and infectious Disease (NIAID); National Institutes of Health (NIH) and US Department of Health and Human Services (DHHS) [grant number U19 AI51794]. FEM-PrEP was conducted under two grants funded by the United States Agency for International Development (USAID): the Contraceptive and Reproductive Health Technologies and Research Utilisation Program (GPO-A-00–05–00022–00), and the Preventive Technologies Agreement (GHO-A-00–09–00016–00). Early support was also provided by the Bill and Melinda Gates Foundation. Gilead Sciences, Inc. donated Truvada® and placebo. LM was supported by the PRF; South African Medical Research Council (MRC); the Carnegie Corporation; the National Research Foundation (NRF) of South Africa and the UCT Clinical Infectious Diseases Research Initiative/Wellcome Trust. No pharmaceutical grants were received in the development of this study.

Stable marital relationship protects men from oral and genital HPV infections

Human papillomavirus (HPV) infections are associated with sexual behavior. Changes in the sexual habits of couples and their impact on male genital and oral HPV infections were determined during 7 years of follow-up (FU). At baseline and 7 years FU, urethral, semen/penile, and oral samples were collected from 46 men and cervical and oral samples of their spouses for HPV DNA detection. Demographic data and risk factors of spouses were recorded by questionnaire at both time points and analyzed for concordance. HPV genotyping was done with the Multimetrix® kit. At baseline, 29.5 % of the male genital and 11 % of their oral samples tested positive. Incident genital HPV infection was found in 23 % and oral infection in 10.9 % of men. Genotype-specific persistence was detected in one man (HPV53) in genital samples. Moderate to almost perfect concordance of changes in sexual habits during FU among spouses were found. Changing partners [p = 0.028; odds ratio (OR) = 15; 95 % confidence interval (CI) 1.355-166.054] and marital status (p = 0.001; 95 % CI 0.000-0.002) increased the risk of incident genital HPV infections. The overall outcome of genital HPV disease in men was linked to the frequency of sexual intercourse (p = 0.023; 95 % CI 0.019-0.026) and changes in marital status (p = 0.022; 95 % CI 0.019-0.026), while oral HPV infections were associated with the number of sexual partners (p = 0.047; 95 % CI 0.041-0.052). Taken together, asymptomatic genital HPV infections among the men were common. The risk of incident genital HPV infections increased among men reporting a change of sexual partner during FU, implicating that a stable marital relationship protects against oral and genital HPV infection.

Semen analysis before and after antibiotic treatment of asymptomatic chlamydia- and ureaplasma-related pyospermia

Pyospermia is the abnormally high concentration of white blood cells in human ejaculate, as caused by a bacterial infection. This study addresses the evaluation of the use of an antibiotic treatment in infertile patients who show asymptomatic pyospermia through the monitoring of semen analysis parameters. The study was carried out on 60 infertile patients who were diagnosed with asymptomatic genital infections, focused on pyospermia caused by Chlamydia trachomatis and Ureaplasma urealyticum. The volume of the ejaculate, pH, sperm concentration and progressive motility, as well as the viability of the spermatozoa and their morphology, were all observed before therapy, 10 and 30days after. Patients were treated with antibiotics in accordance with the recommendations given by the European Urology Association. The results showed a clear effect of antibiotic therapy on the volume and pH of the seminal fluid; moreover, only 30days after completion of the therapy sperm concentration itself significantly increased, and progressive motility greatly improved, albeit slowly. However, it must be noted that the antibiotic therapy had no significant effect on the viability of the spermatozoa within 30days of beginning the treatment.

Associations between Virologic and Immunologic Dynamics in Blood and in the Male Genital Tract

To determine the influence of asymptomatic genital viral infections on the cellular components of semen and blood, we evaluated the associations between the numbers and activation statuses of CD4+ and CD8+ T lymphocytes in both compartments and the seminal levels of cytomegalovirus (CMV), herpes simplex virus (HSV), and human immunodeficiency virus 1 (HIV). Paired blood and semen samples were collected from 36 HIV-infected antiretroviral-naïve individuals and from 40 HIV-uninfected participants. We performed multiparameter flow cytometry analysis (CD45, CD45RA, CD3, CD4, CD8, and CD38) of seminal and blood cellular components and measured HIV RNA and CMV and HSV DNA levels in seminal and blood plasma by real-time PCR. Compared to HIV-uninfected participants, in the seminal compartment HIV-infected participants had higher levels of CMV (P < 0.05), higher numbers of total CD3+ (P < 0.01) and CD8+ subset (P < 0.01) T lymphocytes, and higher CD4+ and CD8+ T lymphocyte activation (RA-CD38+) (P < 0.01). Seminal CMV levels positively correlated with absolute numbers of CD4+ and CD8+ T cells in semen (P < 0.05) and with the activation status of CD4+ T cells in semen and in blood (P < 0.01). HIV levels in semen (P < 0.05) and blood (P < 0.01) were positively associated with T-cell activation in blood. Activation of CD8+ T cells in blood remained an independent predictor of HIV levels in semen in multivariate analysis. The virologic milieu in the male genital tract strongly influences the recruitment and activation of immune cells in semen and may also modulate T-cell immune activation in blood. These factors likely influence replication dynamics, sexual transmission risk, and disease outcomes for all three viruses.

Genital and extra-genital warts increase the risk of asymptomatic genital human papillomavirus infection in men

ObjectivesTo evaluate the relationship of warts in different parts of the body and the risk of asymptomatic genital human papillomavirus (HPV) infection in men.MethodsWe examined the relationship of self-reported genital...

Targeting Trojan Horse leukocytes for HIV prevention

…. is sure design'd, by fraud or force: trust not their presents, nor admit the horse. Virgil, Aeneid Human immunodeficiency virus type 1 (HIV-1), the lymphotropic virus that causes AIDS, has infected more than 60 million people worldwide since its clinical appearance in 1981. Despite intensive prevention efforts, the HIV/AIDS epidemic continues to spread, particularly in developing countries in sub-Saharan Africa, southeast Asia and the Caribbean, as well as the developed world [1]. Although HIV can be transmitted very efficiently parenterally, the advent of routine blood screening prior to transfusion and harm reduction programs for injection drug users, have made this mode of transmission much less common than mucosal transmission. Most new HIV infections are attributable to mucosal transmission: through genital and rectal mucosae in the case of sexual transmission and through oral or gastrointestinal mucosae in the case of mother-to-child transmission [2]. Much has been learned about HIV pathogenesis and infection mechanisms at the molecular level, but the scientific community has yet to develop an effective vaccine or microbicide for HIV prevention. Many unanswered questions remain concerning HIV-1 sexual transmission. In 1983, barely 2 years into the AIDS epidemic, we hypothesized that the agent that was subsequently identified as HIV-1 may be sexually transmitted by infected ‘Trojan Horse’ leukocytes in semen [3]. This hypothesis was based on our knowledge at the time that human semen contains substantial numbers of T lymphocytes and macrophages, which could host a T-cell tropic virus, and the following assumptions: intracellular virus would be better protected than free virus from adverse effects of antiviral factors in the genital environment such as antiviral antibodies likely to be present in genital secretions of the virus-infected transmitter, as well as antimicrobial peptides that play an important role in genital innate immune defense; and virus-infected allogeneic cells could also escape early detection by major histocompatibility complex (MHC)-restricted cytotoxic T cells in a new host. Over the intervening 25+ years, others have also championed this cause [4,5], and convincing evidence has emerged from clinical research as well as in-vitro and animal studies that infected leukocytes indeed play a role in HIV transmission. Yet, most recent research on sexual HIV transmission has focused on cell-free HIV in genital secretions because of the wide availability of HIV RNA quantification assays. Furthermore, the majority of HIV vaccines and microbicides have been designed to block transmission of cell-free virus and have been tested in animal and in-vitro models that use cell-free virus as the only infectious inoculum. As the molecular events underlying cell-associated HIV transmission differ from those underlying cell-free virus transmission, many of the current vaccine and microbicide candidates might not be expected to protect against cell-associated HIV transmission. The failure of several recent vaccine and microbicide clinical trials may be due in part to this oversight. It should be possible to design strategies that block cell-associated HIV transmission as well as cell-free HIV transmission. In this article, we present an overview of research that has been conducted on cell-associated HIV mucosal transmission and recommendations for future research. We focus on sexual HIV transmission, but this review also has relevance for mother-to-child HIV transmission, which may occur through mucosal transmission of cell-associated HIV from maternal genital or mammary gland secretions [6–8]. We review published reports that describe and enumerate HIV-infected cells in genital secretions, and compelling evidence from clinical, animal and in-vitro studies demonstrating that such cells can transmit HIV across genital tract epithelial surfaces; potential molecular mechanisms underlying cell-associated HIV transmission that could be specifically targeted by future HIV prevention strategies; and in-vitro and animal cell-associated HIV transmission models currently used for studies on cell-associated HIV transmission mechanisms and for testing vaccine and microbicide candidates. Using this information as a foundation, we discuss the evidence and probability that various current microbicide and vaccine approaches prevent cell-associated HIV transmission, and suggest additional microbicide and vaccine concepts and experiments that will move this field forward.

Rectovaginal examinations and human papillomavirus: can we decrease the risk of colorectal infection?

Rectovaginal examination with gloves contaminated with vaginal secretions might increase the risk of human papillomavirus (HPV) inoculation of the rectum in women with genital HPV infections. Because of the high prevalence of asymptomatic genital HPV infections, and the association between HPV and colorectal malignancy, examination gloves should be changed between vaginal and rectal examinations.

Asymptomatic genital infection of human papillomavirus in pregnant women and the vertical transmission route.

To further investigate the vertical transmission route of human papillomavirus (HPV) and the indication for the choice of mode of delivery, the infective status of 152 asymptomatic pregnant wemen and the maternal-fetal transmission were studied. By using general primers in polymerase chain reaction (GP-PCR) combined with restriction fragment length polymorphism analysis, HPV DNA positive rate in cervical secretions and venous blood in asymptomatic pregnant women was 36.21% and 52.78%, respectively, and the identified genotypes were mainly HPV16 and 18. The maternal-fetal transmission rate of HPV via genital tract as well as blood was 40.91% and 57. 89%, respectively. It was concluded that besides the transmission route of genital tract and amniotic fluid, there was also transplacental transmission of HPV in utero. Therefore,in our opinion, it is not an absolut indication to perform a cesarean delivery for the pregnant women with HPV asymtomatic genital infection.

Chlamydia trachomatis genital infection in apparently healthy adult population of Tamil Nadu, India: a population-based study.

Since the epidemiology of Chlamydia trachomatis infection in apparently healthy population has not been studied in India, a population-based study was conducted in the state of Tamil Nadu, India in order to analyse the prevalence of genital chlamydial infections in the community and to implement control programmes. A representative sample was taken from three randomly selected districts by using the 'probability proportional to size' cluster survey method. Households were the basic units of clusters. Adults aged 15-45 years, pre-identified from the selected households were enrolled during the medical camps conducted for a major study on community prevalence of sexually transmitted diseases in Tamil Nadu. Blood and urine samples collected from the study subjects were tested by enzyme-linked immunosorbent assay (ELISA) for anti-chlamydial IgM antibodies and by the commercial Amplicor polymerase chain reaction (PCR) test for chlamydial DNA. The prevalence of anti-C. trachomatis antibodies determined by IgM-ELISA was 2.4% (95% CI 1.6%-3.2%). The prevalence of genital chlamydial infection determined by PCR was 1.1% (95% CI 0.5%-1.7%). Majority of the detected infections (68.8%) were asymptomatic. This is the first Indian report on the prevalence of genital chlamydial infections in the general population. It is concluded that this study provides evidence for a substantial burden of approximately 10 million asymptomatic genital chlamydial infection cases in the sexually active age groups in the general population of India.