Baseline HPV prevalence in rectal swabs from men attending a sexual health clinic in Scotland: assessing the potential impact of a selective HPV vaccination programme for men who have sex with men.

OBJECTIVES: A human papillomavirus (HPV) vaccination programme targeted towards men who have sex with men who are disproportionately affected by HPV anogenital infection and related disease was established in Scotland in July 2017. We aimed to establish a baseline HPV prevalence to assess the potential impact of the programme. METHODS: Residual rectal swabs taken in a sexual health clinic (n=1 248) were tested for the presence of HPV and HPV-type prevalence was collated and stratified by age. Prevalence of HPV types included in the quadrivalent and nonavalent vaccines was specifically assessed. RESULTS: 72.8% (95% CI 70.2% to 75.3%) of swabs were positive for HPV with 59.1% (95% CI 56.3% to 61.9%) of samples positive for at least one high-risk type. A least one of HPV 6, 11, 16 and 18 was detected in approximately half of the swabs. HPV prevalence generally increased with age but did not significantly differ between older age groups. The presence of more than one HPV type increased with age and over half of samples had multiple types present. CONCLUSIONS: While HPV prevalence in this population is high, the potential impact of the vaccination programme is substantial given that 50% are not infected with a vaccine type. Defining a preimmunisation baseline in this group will be important for longitudinal monitoring of impact.

Development of an in-house ELISA to detect anti-HPV16-L1 antibodies in serum and dried blood spots.

Measuring anti-HPV antibody levels is important for surveillance of the immunological response to both natural infection and vaccination. Here, an ELISA test for measurement of HPV-16L1 antibodies was developed and validated in sera and dried blood spots. An in-house ELISA was developed for measuring anti-HPV-16L1 IgA and IgG levels. The assay was standardized against WHO international standard serum and validated on serum, dried blood spots and cervical liquid based cytology samples from women attending colposcopy clinics in Scotland. Antibody avidity index was also measured in serum samples. The average HPV 16-L1 specific IgG and IgA levels measured in sera, in women attending a routine colposcopy service were 7.3 units/ml and 8.1 units/ml respectively. Significant correlations between serum and dried blood spot eluates for both IgG and IgA were observed indicating that the latter serve as a credible proxy for antibody levels. Average IgG Avidity Index was 35% (95% CI 25%-45%) suggesting previous, historical challenge with natural infection. This ELISA has potential for use in epidemiological and field studies of antibody prevalence and if coupled with avidity measurement may be of use in individual case monitoring of vaccine responses and failures.

Rapid and robust analytical protocol for E. coli STEC bacteria subspecies differentiation using whole cell MALDI mass spectrometry.

Whole cell MALDI is regularly used for the identification of bacteria to species level in clinical Microbiology laboratories. However, there remains a need to rapidly characterize and differentiate isolates below the species level to support outbreak management. We describe the implementation of a modified preparative approach for MALDI-MS combined with a custom analytical computational pipeline as a rapid procedure for subtyping Shigatoxigenic E. coli (STEC) and accurately identifying strain-specifying biomarkers. The technique was able to differentiate E. coli O157:H7 from other STEC. Within O157 serotype O157:H7 isolates were readily distinguishable from Sorbitol Fermenting O157 isolates. Overall, nine homogeneous groups of isolates were distinguished, each exhibiting distinct profiles of defining mass spectra features. This offers a robust analytical tool useable in reference/diagnostic public health scenarios.

Novel Approaches for Vaccination Against HPV-Induced Cancers.

To date, more than 5 % of all cancers are as a result of human papillomavirus (HPV) infection, and this incidence is increasing. Early recognition of disease is associated with good survival, but late presentation results in devastating consequences. Prevention is better than cure, and there are now successful prophylactic vaccination programmes in place. We discuss these and the prospect of therapeutic vaccinations in the near future to address a growing need for improved therapeutic options.

Human Papillomavirus Prevalence and Herd Immunity after Introduction of Vaccination Program, Scotland, 2009-2013.

In 2008, a national human papillomavirus (HPV) immunization program using a bivalent vaccine against HPV types 16 and 18 was implemented in Scotland along with a national surveillance program designed to determine the longitudinal effects of vaccination on HPV infection at the population level. Each year during 2009-2013, the surveillance program conducted HPV testing on a proportion of liquid-based cytology samples from women undergoing their first cervical screening test for precancerous cervical disease. By linking vaccination, cervical screening, and HPV testing data, over the study period we found a decline in HPV types 16 and 18, significant decreases in HPV types 31, 33, and 45 (suggesting cross-protection), and a nonsignificant increase in HPV 51. In addition, among nonvaccinated women, HPV types 16 and 18 infections were significantly lower in 2013 than in 2009. Our results preliminarily indicate herd immunity and sustained effectiveness of the bivalent vaccine on virologic outcomes at the population level.

Effects of drinking-water filtration on Cryptosporidium seroepidemiology, Scotland.

Continuous exposure to low levels of Cryptosporidium oocysts is associated with production of protective antibodies. We investigated prevalence of antibodies against the 27-kDa Cryptosporidium oocyst antigen among blood donors in 2 areas of Scotland supplied by drinking water from different sources with different filtration standards: Glasgow (not filtered) and Dundee (filtered). During 2006-2009, seroprevalence and risk factor data were collected; this period includes 2007, when enhanced filtration was introduced to the Glasgow supply. A serologic response to the 27-kDa antigen was found for ≈75% of donors in the 2 cohorts combined. Mixed regression modeling indicated a 32% step-change reduction in seroprevalence of antibodies against Cryptosporidium among persons in the Glasgow area, which was associated with introduction of enhanced filtration treatment. Removal of Cryptosporidium oocysts from water reduces the risk for waterborne exposure, sporadic infections, and outbreaks. Paradoxically, however, oocyst removal might lower immunity and increase the risk for infection from other sources.

Estimation of HPV prevalence in young women in Scotland; monitoring of future vaccine impact.

BACKGROUND: Estimation of pre-immunisation prevalence of HPV and distribution of HPV types is fundamental to understanding the subsequent impact of HPV vaccination. We describe the type specific prevalence of HPV in females aged 20-21 in Scotland who attended or defaulted from cervical screening using three specimen types; from attenders liquid based cytology and from defaulters urine or self-taken swabs. METHODS: Residual liquid based cytology samples (n = 2148), collected from women aged 20-21 attending for their first smear were genotyped for HPV. A sample (n = 709) from women who had defaulted from screening was also made available for HPV testing through the use of postal testing kits (either urine samples (n = 378) or self-taken swabs (n = 331)). Estimates of prevalence weighted by deprivation, and for the postal testing kit, also by reminder status and specimen type were calculated for each HPV type. The distribution of HPV types were compared between specimen types and the occurrence of multiple high-risk infections examined. The influence of demographic factors on high-risk HPV positivity and multiple infections was examined via logistic regression. RESULTS: The prevalence of any HPV in young women aged 20-21 was 32.2% for urine, 39.5% for self-taken swab, and 49.4% for LBC specimens. Infection with vaccine specific types (HPV 16, 18) or those associated with cross-protection (HPV 31, 33, 45, 51) was common. Individuals were more likely to test positive for high-risk HPV if they resided in an area of high deprivation or in a rural area. The overall distribution of HPV types did not vary between defaulters and attenders. Multiple infections occurred in 48.1% of high-risk HPV positive individuals. Excluding vaccine types the most common pairing was HPV 56 and 66. CONCLUSIONS: Understanding of the pre-immunisation prevalence of HPV in young women puts Scotland in a prime position to assess the early effect of vaccination as the first highly vaccinated cohorts of individuals enter the screening programme. Differences in results with different specimen types must be taken into account when monitoring the impact of vaccination programmes.

Pathogenic potential to humans of bovine Escherichia coli O26, Scotland.

Escherichia coli O26 and O157 have similar overall prevalences in cattle in Scotland, but in humans, Shiga toxin-producing E. coli O26 infections are fewer and clinically less severe than E. coli O157 infections. To investigate this discrepancy, we genotyped E. coli O26 isolates from cattle and humans in Scotland and continental Europe. The genetic background of some strains from Scotland was closely related to that of strains causing severe infections in Europe. Nonmetric multidimensional scaling found an association between hemolytic uremic syndrome (HUS) and multilocus sequence type 21 strains and confirmed the role of stx(2) in severe human disease. Although the prevalences of E. coli O26 and O157 on cattle farms in Scotland are equivalent, prevalence of more virulent strains is low, reducing human infection risk. However, new data on E. coli O26-associated HUS in humans highlight the need for surveillance of non-O157 enterohemorrhagic E. coli and for understanding stx(2) phage acquisition.

Escherichia coli O157 infection and secondary spread, Scotland, 1999-2008.

To determine the proportion of Escherichia coli O157 cases in Scotland attributable to secondary spread, we analyzed data obtained through entire-population enhanced surveillance. We identified 11% of cases as secondary. Secondary cases in single households were younger than secondary cases in outbreaks affecting >1 household and had similar risk for hemolytic uremic syndrome.

Infection frequently triggers thrombotic microangiopathy in patients with preexisting risk factors: a single-institution experience.

Thrombotic microangiopathies are rare conditions characterized by microangiopathic hemolytic anemia, microthrombi, and multiorgan insult. The disorders, which include hemolytic uremic syndrome and thrombotic thrombocytopenic purpura, are often acute and life threatening. We report a retrospective analysis of 65 patients presenting to our institution from 1997 to 2008 with all forms of thrombotic microangiopathy. Therapeutic plasma exchange was a requirement for analysis and 65 patients were referred to our institution; 66% of patients were female and median age at presentation was 52 years. Bacterial infection was the most commonly identified etiologic factor and in the multivariate model was the only significant variable associated with survival outcome (odds ratio 5.1, 95% confidence interval, 1.2-21.7). As infection can be considered a common trigger event for thrombotic microangiopathy, patients with hepatobiliary sepsis may benefit from elective cholecystectomy. We conclude that bacterial infection frequently triggers TTP and other thrombotic microangiopathies in patients with preexisting risk factors and propose a model for the development of these syndromes.

Emotional and behavioral changes in parents of children affected by hemolytic-uremic syndrome associated with verocytotoxin-producing Escherichia coli: a qualitative analysis.

BACKGROUND: The long-term clinical outcome for children affected by hemolytic uremic syndrome associated with verocytotoxin-producing Escherichia coli (VTEC-HUS) is well documented, but the parental experience is not. OBJECTIVE: The authors investigated the effects of the critical-care hospitalization for this condition on well-being of patients' families. METHOD: A group of 30 parents completed a free-response format survey when their child presented to the hospital; 19 of this cohort completed a 1-year follow-up. RESULTS: Content analysis demonstrated that this cohort of parents experienced long-term emotional distress and substantive disruption to family and daily life. DISCUSSION: These results corroborate anecdotal clinical observations. The authors suggest future research initiatives and best practices to reduce parental distress.

Cryptosporidiosis and filtration of water from Loch Lomond, Scotland.

Previous evidence has suggested an association between consumption of unfiltered water from Loch Lomond, Scotland, and cryptosporidiosis. Before November 1999, this water had been only microstrained and disinfected with chlorine; however, since that time, physical treatment of the water (coagulation, rapid gravity filtration) has been added. To determine risk factors, including drinking water, for cryptosporidiosis, we analyzed data on laboratory-confirmed cases of cryptosporidiosis collected from 1997 through 2003. We identified an association between the incidence of cryptosporidiosis and unfiltered drinking water supplied to the home. The association supports the view that adding a filtration system to minimally treated water can substantially reduce the number of confirmed cryptosporidiosis cases.