Distinguishing importation from diversification of quinolone-resistant Neisseria gonorrhoeae by molecular evolutionary analysis

<p>Abstract</p> <p>Background</p> <p>Distinguishing the recent introduction of quinolone resistant gonococci into a population from diversification of resistant strains already in the population is important for planning effective infection control strategies. We applied molecular evolutionary analyses to DNA sequences from 9 housekeeping genes and <it>gyrA</it>, <it>parC </it>and <it>porB </it>of 24 quinolone resistant <it>N. gonorrhoeae </it>(QRNG) and 24 quinolone sensitive isolates collected in Israel during 2000–2001.</p> <p>Results</p> <p>Phylogenetic and eBURST analyses and estimates of divergence time indicated QRNG were introduced on 3 separate occasions and underwent limited diversification by mutation, deletion and horizontal gene transfer. Reconstruction of <it>N. gonorrhoeae </it>demography showed a slowly declining effective strain population size from 1976 to 1993, rapid decline between 1994 and 1999, and an increase from 1999 to 2001. This is partially attributable to declining gonorrhea case rates from 1973 to 1994. Additional contributing factors are selective sweeps of antibiotic resistant gonococci and increased transmission from sex workers. The abrupt decline in the mid-1990s heralded an increased incidence of gonorrhea from 1997 to the present. The subsequent increase in effective strain population size since 1999 reflects the increased gonococcal census population and introduction of quinolone resistance strains.</p> <p>Conclusion</p> <p>Our study demonstrates the effective use of population genetic approaches to assess recent and historical population dynamics of <it>N. gonorrhoeae</it>.</p

Population genetic estimation of the loss of genetic diversity during horizontal transmission of HIV-1

BACKGROUND: Genetic diversity of the human immunodeficiency virus type 1 (HIV-1) population within an individual is lost during transmission to a new host. The demography of transmission is an important determinant of evolutionary dynamics, particularly the relative impact of natural selection and genetic drift immediately following HIV-1 infection. Despite this, the magnitude of this population bottleneck is unclear. RESULTS: We use coalescent methods to quantify the bottleneck in a single case of homosexual transmission and find that over 99% of the env and gag diversity present in the donor is lost. This was consistent with the diversity present at seroconversion in nine other horizontally infected individuals. Furthermore, we estimated viral diversity at birth in 27 infants infected through vertical transmission and found there to be no difference between the two modes of transmission. CONCLUSION: Assuming the bottleneck at transmission is selectively neutral, such a severe reduction in genetic diversity has important implications for adaptation in HIV-1, since beneficial mutations have a reduced chance of transmission

Age-Specific Human Papillomavirus Antibody and Deoxyribonucleic Acid Prevalence: A Global Review

Global data on human papillomavirus serological and DNA prevalence are essential to optimize HPV prophylactic vaccination strategies

Human papillomavirus types 16, 18, and 31 serostatus and prostate cancer risk in the Prostate Cancer Prevention Trial

Since human papillomavirus (HPV) infection was first identified as a risk factor for cervical cancer, several seroepidemiologic and tissue-based studies have investigated HPV in relation to prostate cancer, another common genitourinary malignancy, with mixed results. To further inform this potential association, we conducted a large, prospective investigation of HPV types 16, 18, and 31 in relation to risk of prostate cancer in the Prostate Cancer Prevention Trial (PCPT). Cases were a sample of men diagnosed with prostate cancer after visit 2 or on their end-of-study biopsy (n=616). Controls were men not diagnosed with prostate cancer during the trial or on their end-of-study biopsy (n=616). Controls were frequency-matched to cases by age, treatment arm, and family history of prostate cancer. Sera from visit 2 were tested for IgG antibodies against HPV-16, -18 and -31. No associations were observed for weak or strong HPV-16 (odds ratio (OR) = 0.94, 95% confidence interval (CI): 0.53–1.64, and OR=1.07, 95% CI: 077–1.48, respectively), HPV-18 (OR=0.75, 95% CI: 0.27–2.04, and OR=0.87, 95% CI: 0.47–1.63) or HPV-31 seropositivity (OR=0.76, 95% CI: 0.45–1.28, and OR=1.15, 95% CI: 0.80–1.64) and risk of prostate cancer. Considering this finding in the context of the HPV and prostate cancer literature, HPV does not appear to be associated with risk of prostate cancer, at least by mechanisms proposed to date, and using epidemiologic designs and laboratory techniques currently available

JC Virus Antibody and Viremia as Predictors of Progressive Multifocal Leukoencephalopathy in Human Immunodeficiency Virus-1-Infected Individuals

We examined whether prediagnostic John Cunningham virus (JCV) antibodies and viremia are predictors of progressive multifocal leukoencephalopathy (PML) in 83 PML cases and 240 human immunodeficiency virus (HIV) disease-matched controls. JCV viremia was not predictive of PML, but some patients showed higher anti-JCV immunoglobulin G (IgG) responses 6 months prior to diagnosi

Rates of New Human Papillomavirus Detection and Loss of Detection in Middle-aged Women by Recent and Past Sexual Behavior.

BACKGROUND: Understanding the source of newly detected human papillomavirus (HPV) in middle-aged women is important to inform preventive strategies, such as screening and HPV vaccination. METHODS: We conducted a prospective cohort study in Baltimore, Maryland. Women aged 35-60 years underwent HPV testing and completed health and sexual behavior questionnaires every 6 months over a 2-year period. New detection/loss of detection rates were calculated and adjusted hazard ratios were used to identify risk factors for new detection. RESULTS: The new and loss of detection analyses included 731 women, and 104 positive for high-risk HPV. The rate of new high-risk HPV detection was 5.0 per 1000 woman-months. Reporting a new sex partner was associated with higher detection rates (adjusted hazard ratio, 8.1; 95% confidence interval, 3.5-18.6), but accounted only for 19.4% of all new detections. Among monogamous and sexually abstinent women, new detection was higher in women reporting ?5 lifetime sexual partners than in those reporting <5 (adjusted hazard ratio, 2.2; 95% confidence interval, 1.2-4.2). CONCLUSION: Although women remain at risk of HPV acquisition from new sex partners as they age, our results suggest that most new detections in middle-aged women reflect recurrence of previously acquired HPV

Population dynamics of Neisseria gonorrhoeae in Shanghai, China: a comparative study

<p>Abstract</p> <p>Background</p> <p>Gonorrhea is a major sexually transmitted disease (STD) in many countries worldwide. The emergence of fluoroquinolone resistance has complicated efforts to control and treat this disease. We report the first study of the evolutionary processes acting on transmission dynamics of a resistant gonococcal population from Shanghai, China. We compare these findings with our previous study of the evolution of a fluoroquinolone sensitive gonococcal population from Baltimore, MD.</p> <p>Methods</p> <p>Ninety six gonococcal samples were collected from male patients in Shanghai, China. All samples were fluoroquinolone resistant. Seven MLST housekeeping genes, two fluoroquinolone resistance genes (<it>gyrA </it>and <it>parC</it>) and the <it>porB </it>gene were sequenced and subjected to population genetic and evolutionary analyses. We estimated genetic diversity, recombination, growth, and selective pressure. The evolutionary history and population dynamics of the Shanghai population were also inferred and compared with that observed in a fluoroquinolone sensitive gonococcal population from Baltimore.</p> <p>Results</p> <p>For both populations, mutation plays a larger role than recombination in the evolution of the <it>porB </it>gene, whereas the latter seems to be the main force driving the evolution of housekeeping and fluoroquinolone resistance genes. In both populations there was evidence for positively selected sites in all genes analyzed. The phylogenetic analyses showed no temporal clustering in the Shanghai gonococcal population, nor did we detect shared allelic profiles between the Shanghai and the Baltimore populations. Past population dynamics of gonococcal strains from Shanghai showed a rising relative effective population size (Ne) in MLST genes with a declining relative Ne for <it>gyrA </it>and <it>parC</it>, whereas among sensitive strains from Baltimore we previously observed concordance among these genes. In both Shanghai and Baltimore, the past population dynamics of gonococcal strains tracked changes in the prevalence of gonorrhea.</p> <p>Conclusions</p> <p>Our study illustrates both similarities and differences in the evolutionary processes acting on gonococcal populations in different geographic areas. An explanation of this pattern that may apply in China is the continued use of quinolone antibiotics despite widespread resistance. Population genetic analysis of gonococcal strains in conjunction with epidemiological surveillance may provide insights into the epidemic behavior of antibiotic resistant strains and help to design control measures.</p

Neutralization Serotyping of BK Polyomavirus Infection in Kidney Transplant Recipients

BK polyomavirus (BKV or BKPyV) associated nephropathy affects up to 10% of kidney transplant recipients (KTRs). BKV isolates are categorized into four genotypes. It is currently unclear whether the four genotypes are also serotypes. To address this issue, we developed high-throughput serological assays based on antibody-mediated neutralization of BKV genotype I and IV reporter vectors (pseudoviruses). Neutralization-based testing of sera from mice immunized with BKV-I or BKV-IV virus-like particles (VLPs) or sera from naturally infected human subjects revealed that BKV-I specific serum antibodies are poorly neutralizing against BKV-IV and vice versa. The fact that BKV-I and BKV-IV are distinct serotypes was less evident in traditional VLP-based ELISAs. BKV-I and BKV-IV neutralization assays were used to examine BKV type-specific neutralizing antibody responses in KTRs at various time points after transplantation. At study entry, sera from 5% and 49% of KTRs showed no detectable neutralizing activity for BKV-I or BKV-IV neutralization, respectively. By one year after transplantation, all KTRs were neutralization seropositive for BKV-I, and 43% of the initially BKV-IV seronegative subjects showed evidence of acute seroconversion for BKV-IV neutralization. The results suggest a model in which BKV-IV-specific seroconversion reflects a de novo BKV-IV infection in KTRs who initially lack protective antibody responses capable of neutralizing genotype IV BKVs. If this model is correct, it suggests that pre-vaccinating prospective KTRs with a multivalent VLP-based vaccine against all BKV serotypes, or administration of BKV-neutralizing antibodies, might offer protection against graft loss or dysfunction due to BKV associated nephropathy