Intrauterine device use, sexually transmitted infections, and fertility: a prospective cohort study.

BACKGROUND: In the 1970s, numerous medical reports, media coverage, and litigation around the Dalkon Shield intrauterine device led to a perception that all intrauterine devices cause upper genital tract infection and infertility. OBJECTIVE: This study aimed to assess the association between intrauterine device use and time to conception. STUDY DESIGN: The Fertility After Contraceptive Termination Study is a multicenter, prospective cohort study of women stopping their contraceptive method to attempt conception. We recruited participants between 2011 and 2017. Participants were a convenience sample of women recruited from academic centers in Philadelphia, PA; Los Angeles, CA; St. Louis, MO; Indianapolis, IN; Aurora, CO; and Salt Lake City, UT. Women were eligible if they stopped their contraceptive method within the past 120 days before enrollment, were between 18 and 35 years of age, had no history of infertility or sterilization, and had at least 6 months of follow-up. Baseline data included demographic and reproductive characteristics, past contraceptive use, nucleic acid amplification testing for sexually transmitted infections, and serology for past infection with Chlamydia trachomatis, Trichomonas vaginalis, and Mycoplasma genitalium. The primary exposure was intrauterine device use (ever); the primary outcome was time to conception. All participants were observed longitudinally for up to 24 months. We used piecewise exponential proportional hazards models with multiple imputation to provide hazard ratios and their respective 95% confidence intervals. RESULTS: Of the 461 participants, mean age was 28.2 years, 178 (38.7%) were Black, 157 (34.1%) were considered as low socioeconomic status, and 275 (59.7%) had a history of intrauterine device use. Without adjusting for any covariates, the median time to conception was shorter for participants who had a history of intrauterine device use (5.1 months) than participants who never used an intrauterine device (7.5 months). After controlling for potential confounders, the association of past intrauterine device use with time to conception was not statistically significant (adjusted hazard ratio, 1.25; 95% confidence interval, 0.99-1.58). In our multivariable model, age, nulligravidity, Black race, low socioeconomic status, and past Mycoplasma genitalium infection were associated with longer times to conception (hazard ratio, 0.76; 95% confidence interval, 0.58-0.99). Conception by 12 months was lower in participants with past Mycoplasma genitalium infection (68% vs 80% without past infection; P=.019). CONCLUSION: We found no impairment of fertility with ever use of an intrauterine device. Serologic evidence of past Mycoplasma genitalium infection was associated with longer times to conception and higher rates of infertility. Mycoplasma genitalium infection is a potential modifiable cause of infertility.

Trichomonas vaginalis exosome-like vesicles modify the cytokine profile and reduce inflammation in parasite-infected mice.

Trichomonas vaginalis (Tv) is a flagellated parasite commonly spread through sexual transmission. This protozoan initiates a severe inflammatory process, inducing nitric oxide, interleukin-6 (IL-6), IL-8, IL-10, IL-17 and IL-22 production by host immune cells. The parasites elicit these responses by releasing surface lipophosphoglycan, small extracellular vesicles (exosomes) and other factors. Tv exosomes are similar to mammalian exosomes and have been implicated in the modulation of IL-8 secretion by epithelial cells. Here, we report that exosome-like vesicles from T. vaginalis (Tv-ELVs) induced a more than 15-fold increase in IL-10 expression in RAW264.7 macrophages but only a two fold increase in IL-6 and TNF-α expression levels measured by RT-PCR. Because Tv-ELVs modulated the macrophage response, we also explored the effect of Tv-ELVs in a murine model of infection. Pretreatment with Tv-ELVs significantly increased IL-10 production as measured in vaginal washes by days 8 and 16 post-infection. Remarkably, Tv-ELVs-pretreated mice exhibited a decrease in IL-17 production and a significant decrease in vulvar inflammation. In addition, IL-6 and IL-13 were decreased during infection. Our results suggest that Tv-ELVs have an immunomodulatory role on the cytokine profile induced by the parasite and promote a decrease in the inflammatory process in mice infected with T. vaginalis.

Trichomonas vaginalis infection induces vaginal CD4+ T-cell infiltration in a mouse model: a vaccine strategy to reduce vaginal infection and HIV transmission.

BACKGROUND: Complications related to the diagnosis and treatment of Trichomonas vaginalis infection, as well as the association between T. vaginalis infection and increased transmission of and susceptibility to human immunodeficiency virus, highlight the need for alternative interventions. We tested a human-safe, aluminum hydroxide-adjuvanted whole-cell T. vaginalis vaccine for efficacy in a BALB/c mouse model of vaginal infection. METHODS: A whole-cell T. vaginalis vaccine was administered subcutaneously to BALB/c mice, using a prime-boost vaccination schedule. CD4(+) T-cell infiltration in the murine vaginal tissue and local and systemic levels of immunoglobulins were measured at time points up to 4 weeks following infection. RESULTS: Vaccination reduced the incidence and increased the clearance of T. vaginalis infection and induced both systemic and local humoral immune responses. CD4(+) T cells were detected in vaginal tissues following intravaginal infection with T. vaginalis but were not seen in uninfected mice. The presence of CD4(+) T cells following T. vaginalis infection can potentially increase susceptibility to and transmission of human immunodeficiency virus. CONCLUSIONS: The vaccine induces local and systemic immune responses and confers significantly greater protection against vaginal infection than seen in unvaccinated mice (P < .005). These data support the potential for a human vaccine against T. vaginalis infection that could also influence the incidence of human immunodeficiency virus infection.

Trichomonas vaginalis origins, molecular pathobiology and clinical considerations.

PURPOSE OF REVIEW: To integrate a selection of the most recent data on Trichomonas vaginalis origins, molecular cell biology and T. vaginalis interactions with the urogenital tract microbiota with trichomoniasis symptoms and clinical management. RECENT FINDINGS: Transcriptomics and proteomics datasets are accumulating, facilitating the identification and prioritization of key target genes to study T. vaginalis pathobiology. Proteins involved in host sensing and cytoskeletal plasticity during T. vaginalis amoeboid transformation were identified. T. vaginalis was shown to secrete exosomes and a macrophage migration inhibitory factor-like protein that both influence host-parasite interactions. T. vaginalis co-infections with Mycoplasma species and viruses were shown to modulate the inflammatory responses, whereas T. vaginalis interactions with various Lactobacillus species inhibit parasite interactions with human cells. T. vaginalis infections were also shown to be associated with bacterial vaginosis. A broader range of health sequelae is also becoming apparent. Diagnostics for both women and men based on the molecular approaches are being refined, in particular for men. SUMMARY: New developments in the molecular and cellular basis of T. vaginalis pathobiology combined with data on the urogenital tract microbiota and immunology have enriched our knowledge on human-microbe interactions that will contribute to increasing our capacity to prevent and treat T. vaginalis and other sexually transmitted infections.

Bacterial vaginosis and the risk of trichomonas vaginalis acquisition among HIV-1-negative women.

BACKGROUND: The vaginal microbiota may play a role in mediating susceptibility to sexually transmitted infections, including Trichomonas vaginalis (TV). METHODS: Data were analyzed from HIV-1-seronegative women participating in HIV Prevention Trials Network Protocol 035. At quarterly visits for up to 30 months, participants completed structured interviews and specimens were collected for genital tract infection testing. T. vaginalis was detected by saline microscopy. Bacterial vaginosis (BV) was characterized by Gram stain using the Nugent score (BV = 7-10; intermediate = 4-6; normal = 0-3 [reference group]). Cox proportional hazards models stratified by study site were used to assess the association between Nugent score category at the prior quarterly visit and TV acquisition. RESULTS: In this secondary analysis, 2920 participants from Malawi, South Africa, United States, Zambia, and Zimbabwe contributed 16,259 follow-up visits. Bacterial vaginosis was detected at 5680 (35%) visits, and TV was detected at 400 (2.5%) visits. Adjusting for age, marital status, hormonal contraceptive use, unprotected sex in the last week and TV at baseline, intermediate Nugent score, and BV at the prior visit were associated with an increased risk of TV (intermediate score: adjusted hazard ratio [aHR], 1.73; 95% confidence interval [CI], 1.21-2.19; BV: aHR, 2.40; 95% CI, 1.92-3.00). Sensitivity analyses excluding 211 participants with TV at baseline were similar to those from the full study population (intermediate score: aHR, 1.54; 95% CI, 1.10-2.14; BV: aHR, 2.23; 95% CI, 1.75-2.84). CONCLUSIONS: Women with a Nugent score higher than 3 were at an increased risk for acquiring TV. If this relationship is causal, interventions that improve the vaginal microbiota could contribute to reductions in TV incidence.

Involvement of mast cells in inflammation induced by Trichomonas vaginalis via crosstalk with vaginal epithelial cells.

Vaginal epithelial cells (VECs) are thought to function as immune-responsive cells in trichomoniasis, and mast cells have been detected in vaginal smears and the vaginal wall in trichomoniasis. It therefore seemed possible that the VEC-trichomonad reaction might affect the activity of mast cells present in the lamina propria of the vaginal mucosa. In this study, we tested whether culture supernatants of VEC incubated with Trichomonas vaginalis (TCM) could stimulate mast cells. When VECs (MS74) were incubated with live trichomonads, IL-8, IL-6 and MCP-1 expressions increased in the TCM, and mast cells (HMC-1) and human neutrophils migrated more actively towards the TCM. Also, when the TCM was added to mast cells, ß-hexosaminidase and cytokines (IL-8 and TNF-α) expressions were increased. Moreover, the culture supernatant of mast cells incubated with TCM (M-TCM) had more increased chemotactic activity for neutrophils than that of TCM. We conclude that inflammatory mediators made by VECs in response to activation by T. vaginalis activate and attract mast cells and then stimulate them to induce neutrophil migration. Our results indicate, for the first time, that VECs play a role in the infiltration of mast cells and neutrophils early in T. vaginalis infection.

Neutrophil interactions with the sexually transmitted parasite Trichomonas vaginalis: implications for immunity and pathogenesis.

Trichomoniasis is the third most common sexually transmitted infection in humans and is caused by the protozoan parasite, Trichomonas vaginalis (Tv). Pathogenic outcomes are more common in women and generally include mild vaginitis or cervicitis. However, more serious effects associated with trichomoniasis include adverse reproductive outcomes. Like other infectious agents, pathogenesis from Tv infection is predicted to be the result of both parasite and host factors. At the site of infection, neutrophils are the most abundant immune cells present and probably play key roles in both parasite clearance and inflammatory pathology. Here, we discuss the evidence that neutrophils home to the site of Tv infection, kill the parasite, and that in some circumstances, parasites possibly evade neutrophil-directed killing. In vitro, the parasite is killed by neutrophils using a novel antimicrobial mechanism called trogocytosis, which probably involves both innate and adaptive immunity. While mechanisms of evasion are mostly conjecture at present, the persistence of Tv infections in patients argues strongly for their existence. Additionally, many strains of Tv harbour microbial symbionts Mycoplasma hominis or Trichomonasvirus, which are both predicted to impact neutrophil responses against the parasite. Novel research tools, especially animal models, will help to reveal the true outcomes of many factors involved in neutrophil-Tv interactions during trichomoniasis.

Structural details and composition of Trichomonas vaginalis lipophosphoglycan in relevance to the epithelial immune function.

Trichomonas vaginalis causes the most common non-viral sexually transmitted infection linked to increased risk of premature birth, cervical cancer and HIV. This study defines molecular domains of the parasite surface glycoconjugate lipophosphoglycan (LPG) with distinct functions in the host immunoinflammatory response. The ceramide phospho-inositol glycan core (CPI-GC) released by mild acid had Mr of approximately 8,700 Da determined by MALDI-TOF MS. Rha, GlcN, Gal and Xyl and small amounts of GalN and Glc were found in CPI-GC. N-acetyllactosamine repeats were identified by endo-beta-galactosidase treatment followed by MALDI-MS and MS/MS and capLC/ESI-MS/MS analyses. Mild acid hydrolysis led to products rich in internal deoxyhexose residues. The CPI-GC induced chemokine production, NF-kappaB and extracellular signal-regulated kinase (ERK)1/2 activation in human cervicovaginal epithelial cells, but neither the released saccharide components nor the lipid-devoid LPG showed these activities. These results suggest a dominant role for CPI-GC in the pathogenic epithelial response to trichomoniasis.

Comparative analysis of the vaginal microbiome of pregnant women with either Trichomonas vaginalis or Chlamydia trachomatis.

BACKGROUND: Although the significance of the human vaginal microbiome for health and disease is increasingly acknowledged, there is paucity of data on the differences in the composition of the vaginal microbiome upon infection with different sexually transmitted pathogens. METHOD: The composition of the vaginal bacterial community of women with Trichomonas vaginalis (TV, N = 18) was compared to that of women with Chlamydia trachomatis (CT, N = 14), and to that of controls (N = 21) (women negative for TV, CT and bacterial vaginosis). The vaginal bacterial composition was determined using high throughput sequencing with the Ion 16S metagenomics kit of the variable regions 2, 4 and 8 of the bacterial 16S ribosomal RNA gene from the vaginal swab DNA extract of the women. QIIME and R package "Phyloseq" were used to assess the α- and ß-diversity and absolute abundance of the 16S rRNA gene per sample in the three groups. Differences in taxa at various levels were determined using the independent T-test. RESULTS: A total of 545 operational taxonomic units (OTUs) were identified in all the three groups of which 488 occurred in all three groups (core OTUs). Bacterial α-diversity, by both Simpson's and Shannon's indices, was significantly higher, (p = 0.056) and (p = 0.001) respectively, among women with either TV or CT than among controls (mean α-diversity TV-infected > CT-infected > Controls). At the genus level, women infected with TV had a significantly (p < 0.01) higher abundance of Parvimonas and Prevotella species compared to both controls and CT-infected women, whereas women infected with CT had a significantly (p < 0.05) higher abundance of Anaerococcus, Collinsella, Corynebacterium and Dialister. CONCLUSION: The vaginal microbiomes of TV and CT-infected women were markedly different from each other and from women without TV and CT. Future studies should determine whether the altered microbiomes are merely markers of disease, or whether they actively contribute to the pathology of the two genital infections.

Among pregnant women with bacterial vaginosis, the hydrolytic enzymes sialidase and prolidase are positively associated with interleukin-1beta.

OBJECTIVE: The objective of the study was to explore the mechanisms of local innate immunity induction and modulation in pregnant women with bacterial vaginosis (BV). STUDY DESIGN: A total of 200 singleton pregnant women in early gestation (12 +/- 4 weeks) with BV (Nugent 7-10) without concurrent vaginal infections with Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, syphilis, and yeast. Concentrations of vaginal interleukin (IL)-1beta and IL-8, the number of neutrophils, and the levels of sialidase and prolidase hydrolytic enzymes were determined in vaginal fluid. RESULTS: Concentrations of vaginal IL-1beta had a strong positive correlation with levels of sialidase (P < .001) and prolidase (P < .001). Conversely, such enzymes were negatively correlated with the ratio of IL-8/IL-1beta (both P < .001) and were not significantly associated with concentrations of IL-8. Notably, the number of vaginal neutrophils had a negative correlation with sialidase (P = .007). CONCLUSION: The strong induction of IL-1beta in BV-positive women appears to be associated with the production of the hydrolytic enzymes sialidase and prolidase by BV-associated bacteria. However, these 2 enzymes may inhibit the expected amplification of the proinflammatory IL-1beta cascade as evaluated by the down-regulation of the IL-8/IL-1beta ratio. A blunted response to IL-1beta signals may cause the poor rise of neutrophils, which is peculiar to BV. This impairment of local defense may contribute to increased susceptibility to adverse outcomes in BV-positive pregnant women.

Trichomonas vaginalis-induced neutrophil apoptosis causes anti-inflammatory cytokine production by human monocyte-derived macrophages.

Neutrophils are the predominant inflammatory cells found in the vaginal discharge of patients with a Trichomonas vaginalis infection. Neutrophils have a shorter life span than other leucocytes. Our previous study indicated that live T. vaginalis alters Mcl-1 expression and caspase-3 activation, thereby inducing apoptosis of human neutrophils. However, it was previously unknown that the apoptotic neutrophils brought about by T. vaginalis can influence vaginal inflammation. Thus, human monocyte-derived macrophages (HMDM) were incubated with T. vaginalis-induced apoptotic neutrophils. Cytokine production and phagocytosis by HMDM were evaluated by ELISA and myeloperoxidase stain, respectively. HMDM showed increased anti-inflammatory cytokine production (IL-10) and decreased levels of pro-inflammatory cytokines, such as TNF-α and IL-6, compared with macrophages alone.

[Killing effect of polymorphonuclear neutrophils on Trichomonas vaginalis].

OBJECTIVE: To study the killing effect of polymorphonuclear neutrophils (PMNs) on Trichomonas vaginalis. METHODS: The vaginal secretion from a patient with vaginitis was incubated in the liver infusion liquid medium to get T. vaginalis. One ml serum was collected from the patient and heated for 30 min at 56 degrees C to inactivate complement in serum, and was absorbed three times with the parasites at 0 degree C to make the serum free of antibodies. PMNs were separated from the patient's blood and purified with density gradient centrifugation and polymer accelerating sedimentation. NBT and safranin O were used to stain the sample. The interaction between PMNs and the parasites was observed under microscope. 300 trichomonads and 3x10(4) PMNs were incubated for 10, 20, 30, 40, 50, 60 minutes under the conditions of aerobic or anaerobic, with superoxide dismutase (SOD) and catalase (CAT) or without SOD and CAT, and with complement or without complement. They were then inoculated in solid medium for another five days under the anaerobic condition, and surviving organisms were enumerated. RESULTS: PMNs were observed to surround and kill a single trichomonad. In the petri-dish containing PMNs, the surviving rate of the parasites in anaerobic condition was 85%, only 3% in aerobic condition (P<0.01). SOD and CAT reduced the killing effect of PMNs, with a surviving rate of 98% and 94% respectively after 60 min incubation. Without SOD and CAT, the surviving rate is only 2% (P<0.05). PMNs in the serum without antibodies killed all the parasites, while the complement-inactivated serum fail to kill them. CONCLUSION: The trichomonacidal activity of PMNs relies on the presence of oxygen and complement in the serum of patient.

Innate host defense of human vaginal and cervical mucosae.

Host defense responses of the human female genital tract mucosa to pathogenic microbes and viruses are mediated in part by the release of antimicrobial substances into the overlying mucosal fluid. While host defense has long been considered a prominent function of vaginal and cervical mucosae, evidence that cationic antimicrobial peptides and proteins have fundamental roles in the innate host defense of this tissue has only recently become available. This chapter explores elements of the physical and chemical defense barriers of the cervicovaginal mucosa, which protect against infections of the lower genital tract. Cationic antimicrobial and antiviral polypeptide components of cervicovaginal fluid are discussed in detail, with special emphasis placed on the defensin family of peptides as well as polypeptides that are active against viruses such as HIV-1. The reader should be cognizant that each polypeptide by itself does not provide complete protection of the genital tract. On the contrary, the abundance and multiplicity of antimicrobial peptides and proteins suggest protection of the cervicovaginal mucosa may be best realized from the aggregate effector molecules.

Host immune consequences of asymptomatic Trichomonas vaginalis infection in pregnancy.

OBJECTIVE: The purpose of this study was to define the impact of asymptomatic trichomoniasis on lower genital tract neutrophil activation in pregnancy. STUDY DESIGN: In this nested cohort study, pelvic examination was performed on 65 asymptomatic pregnant women between 7 and 22 weeks' with vaginal pH > 4.4. Concentrations of cervical interleukin-8 and alpha-defensin were determined using enzyme-linked immunosorbent assay (ELISA). Trichomonas vaginalis was detected by culture. RESULTS: Median concentrations of vaginal fluid neutrophil defensins and cervical interleukin-8 were significantly greater among women with asymptomatic trichomoniasis (median defensins 18,622 ng/mL, median IL-8 9244 pg/mL) than their uninfected counterparts (median defensins 5144 ng/mL, median IL-8 2044 pg/mL) (P < .001). All women with asymptomatic trichomoniasis had detectable defensin and interleukin-8 concentrations. CONCLUSION: Asymptomatic trichomoniasis in pregnancy is accompanied by a state of neutrophil activation.

Rapid Antigen Testing for Trichomoniasis in an Emergency Department.

BACKGROUND AND OBJECTIVES: Trichomoniasis is a prevalent cause of vaginitis among adolescents that increases the risk of acquiring other sexually transmitted diseases and of negative pregnancy outcomes. Treatment of trichomoniasis is therefore essential for improving sexual and reproductive health outcomes. A timely, sensitive diagnostic test for T vaginalis may increase the accuracy of clinician's treatment decisions, resulting in more infected women receiving treatment and fewer uninfected women receiving treatment. METHODS: This study was a retrospective observational assessment of electronic medical records before and after point-of-care (POC) implementation of the rapid antigen test. Records were collected from women aged 14 to 20 years who received a T vaginalis test in the emergency department during either study period. The main outcome measures were rates of accurate treatment, inaccurate treatment, and missed treatment of trichomoniasis in each study period. RESULTS: Overall rates of accurate treatment increased from 78.7% pre-POC to 87.7% post-POC (P = .02). Specifically, rates of not treating uninfected women increased from 61.4% pre-POC to 70.4% post-POC (P = .06), and rates of treating infected women were the same pre-POC (17.3%) and post-POC (17.3%; P = .99). Rates of inaccurate treatment decreased from 23.1% pre-POC to 13.1% post-POC (P = .02). Changes in missed treatment rates (14.0% pre-POC; 8.8% post-POC; P = .73) were not statistically significant. CONCLUSIONS: POC testing can improve clinical care by decreasing the use of antibiotics in uninfected women. The results of this study support the use of a T vaginalis rapid antigen POC test for adolescents presenting to the emergency department.

Intranasal immunisation with a 62 kDa proteinase combined with cholera toxin or CpG adjuvant protects against Trichomonas vaginalis genital tract infections in mice.

Trichomonosis, caused by the protozoan parasite Trichomonas vaginalis, is one of the most frequent sexually transmitted diseases and is widely spread in all continents. Trichomonas vaginalis as well as other protozoan organisms have high levels of proteolitic activity mainly of the cysteine-proteinase type. This activity is necessary for recognition and adhesion of the parasite to the superficial epithelial cells of the host. In the present study, we show that intranasal immunisation with a 62 kDa cysteine-proteinase purified from T. vaginalis excretion-secretion products in combination with cholera toxin or with synthetic oligodeoxynucleotides (ODN) that contain unmethylated CpG motifs (CpG-ODN) elicits 62kDa specific IgG and IgA in vaginal lavage fluid and specific IgG in serum. This immunisation protocol resulted in enhanced elimination of parasites following intravaginal challenge of BALB/c mice.

T. vaginalis Infection Is Associated with Increased IL-8 and TNFr1 Levels but with the Absence of CD38 and HLADR Activation in the Cervix of ESN.

INTRODUCTION: Trichomonas vaginalis infection is associated with an increased risk of HIV infection in exposed-seronegative women (ESN) despite their unique immune quiescent profile. It is important to understand possible mechanisms, such as recruitment of activated T cells, by which T. vaginalis could facilitate HIV infection in this population. METHODS: We conducted a cross-sectional study exploring the relationships between T. vaginalis infection, inflammatory markers and T cell activation in the cervix of ESN. During scheduled study visits, participants completed a behavioral questionnaire and physical exam, including sexually transmitted infection (STI) screening and collection of endocervical sponge and cytobrush specimens. T cell and monocyte phenotypes were measured in cervical cytobrush specimens using multi-parameter flow cytometry. Cervical sponge specimens were used to measure cytokines (IL-6, IL-8,IL-10, IP-10, RANTES) using Luminex immunoassays and the immune activation marker soluble TNF receptor 1 using ELISA. RESULTS: Specimens of 65 women were tested. Twenty-one of these women were infected with T. vaginalis. T. vaginalis infection was associated with significantly increased concentrations of IL-8 (1275pg/ml vs. 566pg/ml, p=.02) and sTNFr1 (430 pg/ml vs. 264 pg/ml, p=.005). However, T. vaginalis infection was not associated with increased percent expression of CCR5+ T cells nor increased CD38 and HLADR activation compared to uninfected women. It was also not associated with increased expression of CCR5+ monocytes. CONCLUSIONS: Among ESN T. vaginalis infection is associated with increased levels of genital pro-inflammatory/immune activation markers IL-8 and TNFr1, but was not associated with an increased percentage of activated endocervical T cells along the CD38 and HLADR pathways. Thus, while T.vaginalis infection may result in some reversal of the immune quiescent profile of ESN, enhanced recruitment of activated CD38 and HLADR expressing CD4+ cells into the endocervix may not be part of the mechanism by which Trichomonas infection alters HIV susceptibility in this unique subset of women.

Evaluating HIV Prevention Programs: Herpes Simplex Virus Type 2 Antibodies as Biomarker for Sexual Risk Behavior in Young Adults in Resource-Poor Countries.

BACKGROUND: Measuring effectiveness of HIV prevention interventions is challenged by bias when using self-reported knowledge, attitude or behavior change. HIV incidence is an objective marker to measure effectiveness of HIV prevention interventions, however, because new infection rates are relatively low, prevention studies require large sample sizes. Herpes simplex virus type 2 (HSV-2) is similarly transmitted and more prevalent and could thus serve as a proxy marker for sexual risk behavior and therefore HIV infection. METHODS: HSV-2 antibodies were assessed in a sub-study of 70,000 students participating in an education intervention in Western Province, Kenya. Feasibility of testing for HSV-2 antibodies was assessed comparing two methods using Fisher's exact test. Three hundred and ninety four students (aged 18 to 22 years) were randomly chosen from the cohort and tested for HIV, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. Out of these, 139 students were tested for HSV-2 with ELISA and surveyed for sexual risk behavior and 89 students were additionally tested for HSV-2 with a point-of-contact (POC) test. RESULTS: Prevalence rates were 0.5%, 1.8%, 0.3% and 2.3% for HIV, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis, respectively. Prevalence of HSV-2 antibodies was 3.4 % as measured by POC test (n=89) and 14.4 % by ELISA (n=139). Specificity of the POC test compared with ELISA was 100%, and the sensitivity only 23.1%. Associations between self-reported sexual behavior and HSV-2 serostatus could not be shown. CONCLUSIONS: Associations between self-reported sexual risk behavior and HSV-2 serostatus could not be shown, probably due to social bias in interviews since its transmission is clearly linked. HSV-2 antibody testing is feasible in resource-poor settings and shows higher prevalence rates than other sexually transmitted diseases thus representing a potential biomarker for evaluation of HIV prevention interventions.

Increased interleukin-10 in the the endocervical secretions of women with non-ulcerative sexually transmitted diseases: a mechanism for enhanced HIV-1 transmission?

OBJECTIVE: Although non-ulcerative sexually transmitted diseases (STD) and bacterial vaginosis are implicated as cofactors in heterosexual HIV-1 transmission, the mechanisms have not been defined. Recent in vitro data suggest that interleukin (IL)-10 may increase susceptibility of macrophages to HIV-1 infection. Therefore, we performed this study to assess whether non-ulcerative STD are associated with detection of IL-10 in the female genital tract. METHODS: Women with clinical pelvic inflammatory disease with or without cervicovaginal discharge were recruited from an STD clinic in Nairobi, Kenya. Endocervical and endometrial specimens were obtained for Neisseria gonorrhoeae and Chlamydia trachomatis DNA detection, Trichonomas vaginalis culture, and CD4 and CD8 T-cell enumeration. Bacterial vaginosis was diagnosed by Gram stain. IL-10 was detected in endocervical specimens using enzyme-linked immunosorbent assay. Blood was obtained for HIV-1 serology. RESULTS: One hundred and seventy-two women were studied. N. gonorrhoeae, C. trachomatis, bacterial vaginosis, and T. vaginalis were detected in 38 (21%), 17 (9%), 71 (43%), and 22 (12%) women, respectively. Cervical IL-10 was detected more often in women with N. gonorrhoeae [adjusted odds ratio (AOR), 3.4; 95% confidence interval (CI), 1.4-8.4], C. trachomatis (AOR, 4.4; 95% CI, 1.2-15.6), and bacterial vaginosis (AOR, 3.1; 95% CI, 1.4-6.9) than in women without these infections. CONCLUSIONS: The association of non-ulcerative STD and bacterial vaginosis with increased frequency of IL-10 detection in endocervical secretions suggests a potential mechanism through which these infections may alter susceptibility to HIV-1 infection in women.

Mechanisms, organisms and markers of infection in pregnancy.

Premature delivery is still a significant problem in Obstetrics. It has multiple causes, with around 50% thought due to infection. Of note infection as a pathogenesis is more likely in those pre-term births occurring <30 weeks gestation and is largely sub-clinical. Potential pathogens largely arise from the ascending route and from the endogenous vaginal flora, causing chorioamnionitis. Resultant morbidity from the release of endo+/exotoxins from such pathogens, the stimulation and production of inflammatory cytokine pathways, prostaglandins, metalloproteinases includes maternal sepsis (chorioamnionitis, septicaemia, post-partum endometritis), pre-term delivery (infant pre-maturity and its consequences, increased susceptibility to cerebral palsy and neonatal sepsis). As well, infection increases mortality due to fetal loss (extreme pre-maturity) as well as severe neonatal sepsis.