Kara Osbak

Recent progress in understanding the epidemiology of bacterial vaginosis.

Purpose of review Bacterial vaginosis epidemiology has been transformed by new theoretical insights and methodologies, such as molecular sequencing. We summarize the progress made in these domains. Recent findings The vaginal microbiome can be classified in five to eight clusters. Bacterial vaginosis-type clusters typically constitute one of these clusters, but in higher risk women, it can constitute up to three clusters. The vaginal microbiomes may be fairly stable or be subject to rapid changes in their constitutive makeup. Bacterial vaginosis does not appear to be a single entity. Certain bacterial communities are associated with particular symptoms of bacterial vaginosis that are paired with unique adverse outcomes. Biofilm-producing Gardnerella vaginalis are likely to play an important role in initiating the structured polymicrobial biofilm that is a hallmark of bacterial vaginosis. Summary Longitudinal studies currently underway should help elucidate how to best define bacterial vaginosis and its subtypes. Risk factors and outcomes associated with particular bacterial vaginosis subtypes should also be further clarified through these studies.

The Global Epidemiology of Syphilis in the Past Century - A Systematic Review Based on Antenatal Syphilis Prevalence.

Background How can we explain the uneven decline of syphilis around the world following the introduction of penicillin? In this paper we use antenatal syphilis prevalence (ASP) to investigate how syphilis prevalence varied worldwide in the past century, and what risk factors correlate with this variance. Methods 1) A systematic review using PubMed and Google Scholar was conducted to identify countries with published data relating to ASP estimates from before 1952 until the present. Eleven countries were identified (Canada, Denmark, Finland, India, Japan, Norway, Singapore, South Africa, United States of America (USA), United Kingdom (UK) and Zimbabwe). The ASP epidemic curve for each population was depicted graphically. In South Africa and the USA, results are reported separately for the black and white populations. 2) National antenatal syphilis prevalence estimates for 1990 to 1999 and 2008 were taken from an Institute for Health Metrics and Evaluation database on the prevalence of syphilis in low risk populations compiled for the Global Burden of Diseases study and from a recent review paper respectively. National ASPs were depicted graphically and regional median ASPs were calculated for both time periods. 3) Linear regression was used to test for an association between ASP in 1990–1999 and 2008 and four risk factors (efficacy of syphilis screening/treatment, health expenditure, GDP per capita and circumcision prevalence). WHO world regions were included as potential explanatory variables. Results In most populations, ASP dropped to under 1% before 1960. In Zimbabwe and black South Africans, ASP was high in the pre-penicillin period, dropped in the post-penicillin period, but then plateaued at around 6% until the end of the 20th century when ASP dropped to just above 1%. In black Americans, ASP declined in the post penicillin period, but plateaued at 3–5% thereafter. ASP was statistically significantly higher in sub-Saharan Africa in 1990–1999 and 2008 than in the other world regions (P < 0.001). On multivariate analysis in both time periods, ASP was only associated with residence in sub-Saharan Africa. Conclusions Further research is necessary to elucidate the reasons for the higher prevalence of syphilis in sub-Saharan Africa.

What underpins the decline in syphilis in Southern and Eastern Africa? An exploratory ecological analysis

BACKGROUND AIDS mortality played an important role in the decline in syphilis prevalence in the USA, but its effect on the dramatic reduction in syphilis prevalence in Southern and Eastern Africa has not been explored. In this ecological study, we investigated the extent to which the relationship between syphilis and HIV prevalence at a population level varied between the early and late periods of the HIV epidemic. METHODS We performed linear regression analysis to measure the association between the national prevalence of syphilis and the peak-HIV prevalence in the early and late phases of the HIV epidemic in 11 countries of Southern and Eastern Africa. RESULTS Our analysis showed a strong positive association between peak-HIV prevalence and syphilis prevalence early in the HIV epidemic (R(2)=0.59; p=0.006). Although only of borderline statistical significance, this linear relationship between HIV prevalence and syphilis prevalence switched to a negative direction late in the HIV epidemic (R(2)=0.32; p=0.07). CONCLUSIONS AIDS mortality may have played an important role in the decline in syphilis in this region. Consequently, with AIDS deaths declining in Sub-Saharan Africa, vigilant surveillance of syphilis prevalence will be necessary to detect a potential re-emergence, as has occurred in high-income countries, and to render a timely public health response.

The Prevalence of HIV by Ethnic Group Is Correlated with HSV-2 and Syphilis Prevalence in Kenya, South Africa, the United Kingdom, and the United States

Background. This paper investigates two issues: do ethnic/racial groups with high HIV prevalences also have higher prevalences of other STIs? and is HIV prevalence by ethnic group correlated with the prevalence of circumcision, concurrency, or having more than one partner in the preceding year? Methods. We used Spearmans correlation to estimate the association between the prevalence of HIV per ethnic/racial group and HSV-2, syphilis, symptoms of an STI, having more than one partner in the past year, concurrency, and circumcision in Kenya, South Africa, the United Kingdom, and the United States. Results. We found that in each country HSV-2, syphilis, and symptomatic STIs were positively correlated with HIV prevalence (HSV-2: Kenya rho = 0.50, P = 0.207; South Africa rho-1, P = 0.000; USA rho-1, P = 0.000, Syphilis: Kenya rho = 0.33, P = 0.420; South Africa rho-1, P = 0.000; USA rho-1, P = 0.000, and STI symptoms: Kenya rho = 0.92, P = 0.001; South Africa rho-1, P = 0.000; UK rho = 0.87, P = 0.058; USA rho-1, P = 0.000). The prevalence of circumcision was only negatively associated with HIV prevalence in Kenya. Both having more than one partner in the previous year and concurrency were positively associated with HIV prevalence in all countries (concurrency: Kenya rho = 0.79, P = 0.036; South Africa rho-1, P = 0.000; UK 0.87, P = 0.058; USA rho-1, P = 0.000 and multiple partners: Kenya rho = 0.82, P = 0.023; South Africa rho-1, P = 0.000; UK rho = 0.87, P = 0.058; USA rho-1, P = 0.000). Not all associations were statistically significant. Conclusion. Further attention needs to be directed to what determines higher rates of partner change and concurrency in communities with high STI prevalence.

The changing relationship between bacterial STIs and HIV prevalence in South Africa – an ecological study

Prevalence estimates of various bacterial sexually transmitted infections in South Africa have declined considerably since the mid-1990s. Syphilis among pregnant women, for example, declined from 10.8% in 1998 to 2.8% in 2001. We used Pearson’s correlation coefficients to estimate the association between the prevalence of syphilis/male urethral discharge/male genital ulcers and the peak HIV prevalence at a district and provincial level in the early and late phases of the HIV epidemic in South Africa. Prevalence estimates of syphilis, male urethral discharge and male genital ulcers during the period preceding the peak HIV prevalence were all positively correlated with the peak HIV prevalence at a provincial level (Pearson’s correlation coefficient [r] = 0.83, p = 0.006; r = 0.66, p = 0.052; r = 0.79, 0.011, respectively). These relationships all switched to a negative association later in the HIV epidemic at a provincial level (r = −0.53, p = 0.14; r = −0.73, p = 0.130; r = −0.54, p = 0.027, respectively). AIDS mortality may have played an important role in the decline of bacterial sexually transmitted infections such as syphilis in this region. Consequently, the relatively recent scale-up of antiretroviral therapy may result in a resurgence of syphilis and other sexually transmitted infections as observed in high-income countries.

Molecular Typing of Syphilis-causing Strains Among Human Immunodeficiency Virus-positive Patients in Antwerp, Belgium

Centers for Disease Control and Prevention and sequencing-based treponeme typing was used to analyze 72 blood samples, collected from human immunodeficiency virus and syphilis co-infected patients during 2014 to 2015 in Antwerp, Belgium. Twenty-nine (40.3%) isolates were polymerase chain reaction positive for Treponema pallidum, and all tested were macrolide-resistant. Four genotypes were identified by sequencing-based typing including two new genotypes, U4NR8 and SU9R8, whereas enhanced Centers for Disease Control and Prevention typing revealed 7 subtypes.

Variations of Sexual Scripts Relating to Concurrency by Race, Class, and Gender in South Africa

It is unclear whether higher rates of sexual partner concurrency in Black South Africans are due to socioeconomic or cultural factors. We used a nationally representative sample of 9,728 individuals aged 16 to 55 from a study conducted in 2009 to examine how the norms pertaining to concurrency and the practice of concurrency vary by race, class, and gender. The percentage of men reporting point concurrency was 14%, 6.5%, and 2.5% in Blacks, coloreds, and Whites, respectively (p < 0.001). These percentages increased to 45.7%, 24.7%, and 11.7%, respectively, for those reporting lifetime concurrency (p < 0.001). In all the racial groups, men exhibited more favorable attitudes toward concurrency than women did. For a range of indicators, White men and women had less favorable attitudes toward concurrency than Black men and women. These differences remained after controlling for a range of confounding variables. In the adjusted logistic regression model, reported concurrency in men was associated with a younger age, Black race, being in the lowest income tertile, not being in a stable relationship, and expressing various positive attitudes toward concurrency.

Characterizing the Syphilis-Causing Treponema pallidum ssp. pallidum Proteome Using Complementary Mass Spectrometry.

Background The spirochete bacterium Treponema pallidum ssp. pallidum is the etiological agent of syphilis, a chronic multistage disease. Little is known about the global T. pallidum proteome, therefore mass spectrometry studies are needed to bring insights into pathogenicity and protein expression profiles during infection. Methodology/Principal Findings To better understand the T. pallidum proteome profile during infection, we studied T. pallidum ssp. pallidum DAL-1 strain bacteria isolated from rabbits using complementary mass spectrometry techniques, including multidimensional peptide separation and protein identification via matrix-assisted laser desorption ionization-time of flight (MALDI-TOF/TOF) and electrospray ionization (ESI-LTQ-Orbitrap) tandem mass spectrometry. A total of 6033 peptides were detected, corresponding to 557 unique T. pallidum proteins at a high level of confidence, representing 54% of the predicted proteome. A previous gel-based T. pallidum MS proteome study detected 58 of these proteins. One hundred fourteen of the detected proteins were previously annotated as hypothetical or uncharacterized proteins; this is the first account of 106 of these proteins at the protein level. Detected proteins were characterized according to their predicted biological function and localization; half were allocated into a wide range of functional categories. Proteins annotated as potential membrane proteins and proteins with unclear functional annotations were subjected to an additional bioinformatics pipeline analysis to facilitate further characterization. A total of 116 potential membrane proteins were identified, of which 16 have evidence supporting outer membrane localization. We found 8/12 proteins related to the paralogous tpr gene family: TprB, TprC/D, TprE, TprG, TprH, TprI and TprJ. Protein abundance was semi-quantified using label-free spectral counting methods. A low correlation (r = 0.26) was found between previous microarray signal data and protein abundance. Conclusions This is the most comprehensive description of the global T. pallidum proteome to date. These data provide valuable insights into in vivo T. pallidum protein expression, paving the way for improved understanding of the pathogenicity of this enigmatic organism.

How many MSM in Europe could benefit from PrEP--a 9 billion Euro question?

Ongoing high HIV incidence among men who have sex with men (MSM) around the world suggests that additional prevention tactics are required. While consistent condom use has been shown to be 80% effective at preventing HIV acquisition (in heterosexual couples), using emtricitabine/tenofovir as oral chemoprophylaxis, also known as pre-exposure-prophylaxis (PrEP), has the potential to be up to 95% efficacious. The deferred arms of two European PrEP studies have recently been stopped due to the effectiveness of PrEP in reducing HIV acquisition. The WHO and the US Centers for Disease Control and Prevention (CDC) have issued guidelines on who should qualify for PrEP, but there has been no indication of what proportion of MSM might meet these criteria. In this paper, we assess what proportion of MSM who participated in the European MSM Internet Survey (EMIS) would qualify for PrEP based on the CDC guidelines, which were chosen as they are the most comprehensive available guidelines. We close by suggesting a twopronged approach to ensure optimal PrEP availability for MSM. The detailed methods of EMIS have been reported elsewhere. In brief, EMIS was an anonymous, selfadministered online survey conducted simultaneously in 25 languages across 38 countries, with a final sample size of 174,209 respondents. Participants were recruited through more than 230 social media/dating websites for MSM. Typical completion time was 20min. No financial incentives were given. No IP addresses were collected. The survey was accessible online from 6 June to 31 August, 2010. More background information, including the English version of the questionnaire, is available at www.emis-project.eu. After exclusion of 6013 respondents (3.5%) who were under 18 years old or reported never having had sex with men, and 1724 (1.0%) with missing data on HIV-testing history or sexual behaviour, the analytic sample includes 166,472 MSM (95.6%). The number of MSM in the 38 EMIS countries and the European Union who are eligible for PrEP according to the CDC are calculated by applying the eligibility criteria to the estimated MSM populations in each country. As national response rates across the 38 included countries differ substantially, country medians are reported. CDC guidelines recommend PrEP for MSM who are adult, HIV negative, have had a male sex partner in the past six months, are not in a mutually monogamous relationship with a recently tested HIV-negative man and at least one of the following:

Repeat syphilis has a different immune response compared with initial syphilis: an analysis of biomarker kinetics in two cohorts

Objective We aimed to asses if there are differences in the clinical presentation and immune response of repeat as compared with initial syphilis. Methods Prospective study: we prospectively recruited all patients with a new diagnosis of syphilis and tested their plasma for a range of cytochemokines and rapid plasma reagin (RPR) at baseline pretreatment and 6 months following therapy. Retrospective study: we compared RPR assay response kinetics between initial and repeat syphilis in persons attending our HIV/STI clinic from 1993 to 2016. Results Prospective study: a total of 91 individuals, 36 with initial syphilis and 55 with repeat syphilis, were included in the study. At baseline visit, those with initial syphilis were more likely to be symptomatic and have higher levels of interleukin-10 than repeaters. At baseline, median RPR titres were higher in the repeat than the initial infection groups. Repeaters were less likely than those with initial infections to serorevert to a negative RPR and be serofast (<4-fold RPR titre decline) at 6 months. Retrospective study: syphilis was diagnosed in 1027/43 870 individuals tested. At diagnosis, repeaters had higher RPR titres and a stepwise increase in RPR titre with number of syphilis episodes. They had a different RPR test response kinetic: they were less likely to be serofast and to serorevert than initial syphilis at 6 and 12 months. No individuals with four or more previous episodes of syphilis seroreverted. Conclusion Repeat syphilis has a different clinical presentation and immunological response to initial infection.