Emerging Infectious Diseases Are Virulent Viruses-Are We Prepared? An Overview.

The recent pandemic caused by SARS-CoV-2 affected the global population, resulting in a significant loss of lives and global economic deterioration. COVID-19 highlighted the importance of public awareness and science-based decision making, and exposed global vulnerabilities in preparedness and response systems. Emerging and re-emerging viral outbreaks are becoming more frequent due to increased international travel and global warming. These viral outbreaks impose serious public health threats and have transformed national strategies for pandemic preparedness with global economic consequences. At the molecular level, viral mutations and variations are constantly thwarting vaccine efficacy, as well as diagnostic, therapeutic, and prevention strategies. Here, we discuss viral infectious diseases that were epidemic and pandemic, currently available treatments, and surveillance measures, along with their limitations.

Tobacco Use and Prevalence of Human Papillomavirus in Self-Collected Cervicovaginal Swabs Between 2009 and 2014.

OBJECTIVE: To evaluate relationships between an objective biomarker of current tobacco exposure and high-risk genital human papillomavirus (HPV) prevalence among adult women in the United States. METHODS: We performed a retrospective analysis of adult women (aged 18-59 years) using three consecutive 2-year cycles (2009-2014) from the cross-sectional National Health and Nutrition Examination Surveys. Women who provided self-collected cervicovaginal swabs and serum were included. Human papillomavirus genotyping was conducted on cervicovaginal samples with a Linear Array HPV assay. Cotinine, a major metabolite of nicotine, was assayed from serum to provide a biomarker of recent tobacco exposure. Participants were stratified into three levels of tobacco exposure (nonsmokers, secondhand smoke exposure, and smokers) based on serum cotinine concentration levels using previously published ethnic-specific cut points. Weighted percentages are provided to account for unequal selection probabilities among participants and adjustments for nonresponse. RESULTS: Among the 5,158 women analyzed, 2,778 were classified as nonsmokers (57.1%, 95% CI 54.5-59.6%), 1,109 classified as having secondhand smoke exposure (18.4%, 95% CI 16.5-20.3%), and 1,271 classified as smokers (24.6%, 95% CI 22.8-26.5%) using serum cotinine concentration levels. Prevalence of HPV infection differed between nicotine exposure groups (P<.001): 441 smokers (32.1%, 95% CI 29.6-34.7%), 322 women with secondhand smoke exposure (26.1%, 95% CI 22.7-29.7%), and 451 nonsmokers (15.1%, 95% CI 13.3-17.1%) had a high-risk genital HPV infection. Controlling for demographics and number of lifetime sexual partners, the risks compared with nonsmokers for infection with a high-risk HPV genotype for smokers (adjusted odds ratio [OR] 1.7, 95% CI 1.4-22) and secondhand smokers (adjusted OR 1.4, 95% CI 1.1-1.8) are similarly increased (P<.001). CONCLUSION: In this large cross-sectional, population-based study, we show a relationship between an objective biomarker of current tobacco use and genital HPV infection. Cigarette smoking and exposure to secondhand smoke are associated with increased odds of infection with high-risk genital HPV independent of lifetime number of sexual partners.

Variation in genital human papillomavirus infection prevalence and vaccination coverage among men and women in the USA.

Human papillomavirus (HPV) is the most common sexually transmitted infection that causes majority of anogenital and oropharyngeal cancers. Prophylactic HPV vaccine is available for the primary prevention of cancer and HPV transmission. Here, we are going to discuss the variation of HPV prevalence, HPV vaccination coverage and potential risk factors of men and women, retrieved from the cross-sectional study of the National Health Nutrition Examination Survey, a representative sample of noninstitutionalized, civilian residents in the USA. The overall penile HPV prevalence in men was 45.2% and the high risk oncogenic HPV prevalence defined by DNA testing was 25.1% that appeared to be widespread among all the age groups, which contrasts the vaginal HPV prevalence of 26.8% in women.

Prevalence of Genital Human Papillomavirus Infection and Human Papillomavirus Vaccination Rates Among US Adult Men: National Health and Nutrition Examination Survey (NHANES) 2013-2014.

IMPORTANCE: Human papillomavirus (HPV) is a common sexually transmitted infection that is a major cause of noncervical anogenital and oropharyngeal cancers. Prophylactic HPV vaccine is available for primary prevention. However, the population prevalence data for male genital HPV infection is not well known, while the HPV vaccination coverage is low in the United States. OBJECTIVES: To estimate the prevalence of genital HPV infection and the HPV vaccination rate in the United States among adult men and to examine potential risk factors for HPV infection. DESIGN, SETTING, AND PARTICIPANTS: The National Health and Nutrition Examination Survey (NHANES) samples a representative cross-section of the US population. Men aged 18 to 59 years were examined in mobile examination centers during the NHANES 2013-2014. DNA was extracted from self-collected penile swab specimens, and HPV genotyping was performed by polymerase chain reaction amplification. Demographic and vaccination information was gathered via self-report during home-based standardized interviews. Binary multivariable logistic regression was used to estimate the odds of HPV infection. MAIN OUTCOMES AND MEASURES: The prevalence of genital HPV infection and the HPV vaccination coverage rate among adult men. RESULTS: During the NHANES 2013-2014, a total of 1868 men aged 18 to 59 years were examined. The overall genital HPV infection prevalence was 45.2% (95% CI, 41.3%-49.3%). The infection prevalence with at least 1 high-risk HPV subtype defined by DNA testing was 25.1% (95% CI, 23.0%-27.3%). In vaccine-eligible men, the prevalence of infection with at least 1 HPV strain targeted by the HPV 4-valent vaccine and HPV 9-valent vaccine was 7.1% (95% CI, 5.1%-9.5%) and 15.4% (95% CI, 11.7%-19.6%), respectively. Among vaccine-eligible men, the HPV vaccination coverage was 10.7% (95% CI, 7.8%-14.6%). CONCLUSIONS AND RELEVANCE: Among men aged 18 to 59 years in the United States, the overall prevalence of genital HPV infection was 45.2% (95% CI, 41.3%-49.3%). The overall genital HPV infection prevalence appears to be widespread among all age groups of men, and the HPV vaccination coverage is low.

Proteomics and biomarkers in clinical trials for drug development.

Proteomics allows characterization of protein structure and function, protein-protein interactions, and peptide modifications. It has given us insight into the perturbations of signaling pathways within tumor cells and has improved the discovery of new therapeutic targets and possible indicators of response to and duration of therapy. The discovery, verification, and validation of novel biomarkers are critical in streamlining clinical development of targeted compounds, and directing rational treatments for patients whose tumors are dependent upon select signaling pathways. Studies are now underway in many diseases to examine the immune or inflammatory proteome, vascular proteome, cancer or disease proteome, and other subsets of the specific pathology microenvironment. Successful assay verification and biological validation of such biomarkers will speed development of potential agents to targetable dominant pathways and lead to selection of individuals most likely to benefit. Reconsideration of analytical and clinical trials methods for acquisition, examination, and translation of proteomics data must occur before we march further into future of drug development.

The value of repeated cytology at the time of first colposcopy: a retrospective analysis of 1,087 cases.

Papanicolaou tests are often repeated just before the procedure for women who have been referred for colposcopy. The validity and clinical usefulness of this practice, however, is unclear. We retrospectively assessed the value of repeated cytology in a cohort of 1,087 consecutive patients who underwent repeated Papanicolaou testing at first colposcopy. The repeated cytology was considered clinically useful if the results could conceivably have influenced the physician's decision about more invasive diagnostic/therapeutic evaluation based on contemporary practice guidelines. Repeated cytology provided potentially clinically useful information in only a small proportion (3.6%) of the cases analyzed overall, including 41% (26/63) and 1.8% of the high- and low-grade squamous intraepithelial lesions referral cytology cases, respectively. Our data indicate that repeated cytology provides potentially clinically useful information in only a small percentage of overall cases but a substantial proportion of high-grade squamous intraepithelial lesion referral cytology cases, suggesting that high-risk referral cytology case subsets can be defined wherein the routine performance of repeated cytology would be most efficacious.

Progranulin is a potential prognostic biomarker in advanced epithelial ovarian cancers.

OBJECTIVE: There are few validated relapse prediction biomarkers for epithelial ovarian cancer (EOC). We have shown progranulin (PGRN) and secretory leukocyte protease inhibitor (SLPI) are up regulated, overexpressed survival factors in EOC. We hypothesized they would predict presence of occult EOC. METHOD: PGRN, SLPI, and the known biomarker HE4 were measured in EOC patient plasma samples, prospectively collected every 3 months from initial remission until relapse. Clinical data and CA125 results were incorporated into statistical analyses. Exploratory Kaplan-Meier estimates, dividing markers at median values, evaluated association with progression-free survival (PFS) and overall survival (OS). Area-under-the-curve (AUC) statistics were computed from receiver operating characteristic (ROC) curves to evaluate discrimination ability. A Cox proportional hazards model assessed the association between PFS, OS, and biomarkers, adjusting for clinical prognostic factors. RESULTS: Samples from 23 advanced stage EOC patients were evaluated. PGRN at 3 months was the only biomarker independently associated with PFS (P<0.0001) and OS (P<0.003). When used to predict progression by 18 months, sensitivity and specificity were 93% and 100%, respectively, with AUC=0.944. The Cox model hazard ratio for PFS, divided at 59 ng/ml by ROC analysis and adjusted for clinical factors, was 23.5 (95% CI: 2.49-220). Combinations with SLPI, HE4, and/or CA125 did not improve the model. CONCLUSIONS: We report pilot data indicating a potential independent association of PGRN on EOC patient PFS and OS. A validation study will be required to confirm this finding and to inform whether PGRN warrants evaluation as a potential screening biomarker.