Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses

G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattle-infecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NF\u3baB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5'-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place

Swine-Origin Influenza A Outbreak 2009 at Shinshu University, Japan

<p>Abstract</p> <p>Background</p> <p>A worldwide outbreak of swine flu H1N1 pandemic influenza occurred in April 2009. To determine the mechanism underlying the spread of infection, we prospectively evaluated a survey implemented at a local university.</p> <p>Methods</p> <p>Between August 2009 and March 2010, we surveyed 3 groups of subjects: 2318 children in six schools attached to the Faculty of Education, 11424 university students, and 3344 staff members. Subjects with influenza-like symptoms who were diagnosed with swine flu at hospitals or clinics were defined as swine flu patients and asked to make a report using a standardized form.</p> <p>Results</p> <p>After the start of the pandemic, a total of 2002 patients (11.7%) were registered in the survey. These patients included 928 schoolchildren (40.0%), 1016 university students (8.9%), and 58 staff members (1.7%). The incidence in schoolchildren was significantly higher than in the other 2 groups (<it>P </it>< 0.0001) but there were no within group differences in incidence rate between males and females. During the period of the survey, three peaks of patient numbers were observed, in November 2009, December 2009, and January 2010. The first peak consisted mainly of schoolchildren, whereas the second and third peaks included many university students. Staff members did not contribute to peak formation. Among the university students, the most common suspected route of transmission was club activity. Interventions, such as closing classes, schools, and clubs, are likely to affect the epidemic curves.</p> <p>Conclusion</p> <p>Schoolchildren and university students are vulnerable to swine flu, suggesting that avoidance of close contact, especially among these young people, may be effective way in controlling future severe influenza pandemics, especially at educational institutions.</p

Dengue in Madeira Island

This is a preprint of a paper whose final and definite form will be published in the volume Mathematics of Planet Earth that initiates the book series CIM Series in Mathematical Sciences (CIM-MS) published by Springer. Submitted Oct/2013; Revised 16/July/2014 and 20/Sept/2014; Accepted 28/Sept/2014.Dengue is a vector-borne disease and 40% of world population is at risk. Dengue transcends international borders and can be found in tropical and subtropical regions around the world, predominantly in urban and semi-urban areas. A model for dengue disease transmission, composed by mutually-exclusive compartments representing the human and vector dynamics, is presented in this study. The data is from Madeira, a Portuguese island, where an unprecedented outbreak was detected on October 2012. The aim of this work is to simulate the repercussions of the control measures in the fight of the disease

Variability in transmissibility of the 2009 H1N1 pandemic in Canadian communities

Abstract Background The prevalence and severity of the 2009 H1N1 pandemic appeared to vary significantly across populations and geographic regions. We sought to investigate the variability in transmissibility of H1N1 pandemic in different health regions (including urban centres and remote, isolated communities) in the province of Manitoba, Canada. Methods The Richards model was used to fit to the daily number of laboratory-confirmed cases and estimate transmissibility (referred to as the basic reproduction number, R0), doubling times, and turning points of outbreaks in both spring and fall waves of the H1N1 pandemic in several health regions. Results We observed considerable variation in R0 estimates ranging from 1.55 to 2.24, with confidence intervals ranging from 1.45 to 2.88, for an average generation time of 2.9 days, and shorter doubling times in some remote and isolated communities compared to urban centres, suggesting a more rapid spread of disease in these communities during the first wave. For the second wave, R e , the effective reproduction number, is estimated to be lower for remote and isolated communities; however, outbreaks appear to have been driven by somewhat higher transmissibility in urban centres. Conclusions There was considerable geographic variation in transmissibility of the 2009 pandemic outbreaks. While highlighting the importance of estimating R0 for informing health responses, the findings indicate that projecting the transmissibility for large-scale epidemics may not faithfully characterize the early spread of disease in remote and isolated communities

Risk Factors and Immunity in a Nationally Representative Population following the 2009 Influenza A(H1N1) Pandemic

Understanding immunity, incidence and risk factors of the 2009 influenza A(H1N1) pandemic (2009 H1N1) through a national seroprevalence study is necessary for informing public health interventions and disease modelling.We collected 1687 serum samples and individual risk factor data between November-2009 to March-2010, three months after the end of the 2009 H1N1 wave in New Zealand. Participants were randomly sampled from selected general practices countrywide and hospitals in the Auckland region. Baseline immunity was measured from 521 sera collected during 2004 to April-2009. Haemagglutination inhibition (HI) antibody titres of ≥1∶40 against 2009 H1N1 were considered seroprotective as well as seropositive. The overall community seroprevalence was 26.7% (CI:22.6–29.4). The seroprevalence varied across age and ethnicity. Children aged 5–19 years had the highest seroprevalence (46.7%;CI:38.3–55.0), a significant increase from the baseline (14%;CI:7.2–20.8). Older adults aged ≥60 had no significant difference in seroprevalence between the serosurvey (24.8%;CI:18.7–30.9) and baseline (22.6%;CI:15.3–30.0). Pacific peoples had the highest seroprevalence (49.5%;CI:35.1–64.0). There was no significant difference in seroprevalence between both primary (29.6%;CI:22.6–36.5) and secondary healthcare workers (25.3%;CI:20.8–29.8) and community participants. No significant regional variation was observed. Multivariate analysis indicated age as the most important risk factor followed by ethnicity. Previous seasonal influenza vaccination was associated with higher HI titres. Approximately 45.2% of seropositive individuals reported no symptoms.Based on age and ethnicity standardisation to the New Zealand Population, about 29.5% of New Zealanders had antibody titers at a level consistent with immunity to 2009 H1N1. Around 18.3% of New Zealanders were infected with the virus during the first wave including about one child in every three. Older people were protected due to pre-existing immunity. Age was the most important factor associated with infection followed by ethnicity. Healthcare workers did not appear to have an increased risk of infection compared with the general population

Climatic Factors Driving Invasion of the Tiger Mosquito (Aedes albopictus) into New Areas of Trentino, Northern Italy

Background:The tiger mosquito (Aedes albopictus), vector of several emerging diseases, is expanding into more northerly latitudes as well as into higher altitudes in northern Italy. Changes in the pattern of distribution of the tiger mosquito may affect the potential spread of infectious diseases transmitted by this species in Europe. Therefore, predicting suitable areas of future establishment and spread is essential for planning early prevention and control strategies.Methodology/Principal Findings:To identify the areas currently most suitable for the occurrence of the tiger mosquito in the Province of Trento, we combined field entomological observations with analyses of satellite temperature data (MODIS Land Surface Temperature: LST) and human population data. We determine threshold conditions for the survival of overwintering eggs and for adult survival using both January mean temperatures and annual mean temperatures. We show that the 0°C LST threshold for January mean temperatures and the 11°C threshold for annual mean temperatures provide the best predictors for identifying the areas that could potentially support populations of this mosquito. In fact, human population density and distance to human settlements appear to be less important variables affecting mosquito distribution in this area. Finally, we evaluated the future establishment and spread of this species in relation to predicted climate warming by considering the A2 scenario for 2050 statistically downscaled at regional level in which winter and annual temperatures increase by 1.5 and 1°C, respectively.Conclusions/Significance:MODIS satellite LST data are useful for accurately predicting potential areas of tiger mosquito distribution and for revealing the range limits of this species in mountainous areas, predictions which could be extended to an European scale. We show that the observed trend of increasing temperatures due to climate change could facilitate further invasion of Ae. albopictus into new areas. © 2011 Roiz et al.Peer Reviewe

HIV and pre-neoplastic and neoplastic lesions of the cervix in South Africa: a case-control study

BACKGROUND: Cervical cancer and infection with human immunodeficiency virus (HIV) are both major public health problems in South Africa. The aim of this study was to determine the risk of cervical pre-cancer and cancer among HIV positive women in South Africa. METHODS: Data were derived from a case-control study that examined the association between hormonal contraceptives and invasive cervical cancer. The study was conducted in the Western Cape (South Africa), from January 1998 to December 2001. There were 486 women with invasive cervical cancer, 103 control women with atypical squamous cells of undetermined significance (ASCUS), 53 with low-grade squamous intraepithelial lesions (LSIL), 50 with high-grade squamous intraepithelial lesions (HSIL) and 1159 with normal cytology. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multiple logistic regression. RESULTS: The adjusted odds ratios associated with HIV infection were: 4.4 [95% CI (2.3 – 8.4) for ASCUS, 7.4 (3.5 – 15.7) for LSIL, 5.8 (2.4 – 13.6) for HSIL and 1.17 (0.75 – 1.85) for invasive cervical cancer. HIV positive women were nearly 5 times more likely to have high-risk human papillomavirus infection (HR-HPV) present compared to HIV negative women [OR 4.6 (95 % CI 2.8 – 7.5)]. Women infected with both HIV and high-risk HPV had a more than 40 fold higher risk of SIL than women infected with neither of these viruses. CONCLUSION: HIV positive women were at an increased risk of cervical pre-cancer, but did not demonstrate an excess risk of invasive cervical cancer. An interaction between HIV and HR-HPV infection was demonstrated. Our findings underscore the importance of developing locally relevant screening and management guidelines for HIV positive women in South Africa

An Ecological Study of the Determinants of Differences in 2009 Pandemic Influenza Mortality Rates between Countries in Europe

Pandemic A (H1N1) 2009 mortality rates varied widely from one country to another. Our aim was to identify potential socioeconomic determinants of pandemic mortality and explain between-country variation.Based on data from a total of 30 European countries, we applied random-effects Poisson regression models to study the relationship between pandemic mortality rates (May 2009 to May 2010) and a set of representative environmental, health care-associated, economic and demographic country-level parameters. The study was completed by June 2010.Most regression approaches indicated a consistent, statistically significant inverse association between pandemic influenza-related mortality and per capita government expenditure on health. The findings were similar in univariable [coefficient: -0.00028, 95% Confidence Interval (CI): -0.00046, -0.00010, p = 0.002] and multivariable analyses (including all covariates, coefficient: -0.00107, 95% CI: -0.00196, -0.00018, p = 0.018). The estimate was barely insignificant when the multivariable model included only significant covariates from the univariate step (coefficient: -0.00046, 95% CI: -0.00095, 0.00003, p = 0.063).Our findings imply a significant inverse association between public spending on health and pandemic influenza mortality. In an attempt to interpret the estimated coefficient (-0.00028) for the per capita government expenditure on health, we observed that a rise of 100 international dollars was associated with a reduction in the pandemic influenza mortality rate by approximately 2.8%. However, further work needs to be done to unravel the mechanisms by which reduced government spending on health may have affected the 2009 pandemic influenza mortality

First Report of Sylvatic DENV-2-Associated Dengue Hemorrhagic Fever in West Africa

Dengue virus (DENV) circulates in human and sylvatic cycles. Sylvatic strains are both ecologically and evolutionarily distinct from endemic viruses. Although sylvatic dengue cycles occur in West African countries and Malaysia, only a few cases of mild human disease caused by sylvatic strains and one single case of dengue hemorrhagic fever in Malaysia have been reported. Here we report a case of dengue hemorrhagic fever (DHF) with thrombocytopenia (13000/µl), a raised hematocrit (32% above baseline) and mucosal bleeding in a 27-year-old male returning to Spain in November 2009 after visiting his home country Guinea Bissau. Sylvatic DENV-2 West African lineage was isolated from blood and sera. This is the first case of DHF associated with sylvatic DENV-2 in Africa and the second case worldwide of DHF caused by a sylvatic strain

The Chikungunya Epidemic on La Réunion Island in 2005–2006: A Cost-of-Illness Study

For a long time, studies of chikungunya virus infection have been neglected, but since its resurgence in the south-western Indian Ocean and on La Réunion Island, this disease has been paid greater amounts of attention. The economic and social impacts of chikungunya epidemics are poorly documented, including in developed countries. This study estimated the cost-of-illness associated with the 2005–2006 chikungunya epidemics on La Réunion Island, a French overseas department with an economy and health care system of a developed country. “Cost-of-illness” studies measure the amount that would have been saved in the absence of a disease. We found that the epidemic incurred substantial medical expenses estimated at €43.9 million, of which 60% were attributable to direct medical costs related, in particular, to expenditure on medical consultations (47%), hospitalization (32%) and drugs (19%). The costs related to care in ambulatory and hospitalized cases were €90 and €2000 per case, respectively. This study provides the basic inputs for conducting cost-effectiveness and cost-benefit evaluations of chikungunya prevention strategies