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The American Journal of Tropical... Nov 2015Pinta is a neglected, chronic skin disease that was first described in the sixteenth century in Mexico. The World Health Organization lists 15 countries in Latin America...
Pinta is a neglected, chronic skin disease that was first described in the sixteenth century in Mexico. The World Health Organization lists 15 countries in Latin America where pinta was previously endemic. However, the current prevalence of pinta is unknown due to the lack of surveillance data. The etiological agent of pinta, Treponema carateum, cannot be distinguished morphologically or serologically from the not-yet-cultivable Treponema pallidum subspecies that cause venereal syphilis, yaws, and bejel. Although genomic sequencing has enabled the development of molecular techniques to differentiate the T. pallidum subspecies, comparable information is not available for T. carateum. Because of the influx of migrants and refugees from Latin America, U.S. physicians should consider pinta in the differential diagnosis of skin diseases in children and adolescents who come from areas where pinta was previously endemic and have a positive reaction in serological tests for syphilis. All stages of pinta are treatable with a single intramuscular injection of penicillin.
Topics: Anti-Bacterial Agents; Humans; Latin America; Neglected Diseases; Penicillin G Benzathine; Phylogeny; Pinta; Treponema
PubMed: 26304920
DOI: 10.4269/ajtmh.15-0329 -
The New England Journal of Medicine May 2015In previous phase 1-2 clinical trials involving older adults, a subunit vaccine containing varicella-zoster virus glycoprotein E and the AS01B adjuvant system (called... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In previous phase 1-2 clinical trials involving older adults, a subunit vaccine containing varicella-zoster virus glycoprotein E and the AS01B adjuvant system (called HZ/su) had a clinically acceptable safety profile and elicited a robust immune response.
METHODS
We conducted a randomized, placebo-controlled, phase 3 study in 18 countries to evaluate the efficacy and safety of HZ/su in older adults (≥50 years of age), stratified according to age group (50 to 59, 60 to 69, and ≥70 years). Participants received two intramuscular doses of the vaccine or placebo 2 months apart. The primary objective was to assess the efficacy of the vaccine, as compared with placebo, in reducing the risk of herpes zoster in older adults.
RESULTS
A total of 15,411 participants who could be evaluated received either the vaccine (7698 participants) or placebo (7713 participants). During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001). Vaccine efficacy was between 96.6% and 97.9% for all age groups. Solicited reports of injection-site and systemic reactions within 7 days after vaccination were more frequent in the vaccine group. There were solicited or unsolicited reports of grade 3 symptoms in 17.0% of vaccine recipients and 3.2% of placebo recipients. The proportions of participants who had serious adverse events or potential immune-mediated diseases or who died were similar in the two groups.
CONCLUSIONS
The HZ/su vaccine significantly reduced the risk of herpes zoster in adults who were 50 years of age or older. Vaccine efficacy in adults who were 70 years of age or older was similar to that in the other two age groups. (Funded by GlaxoSmithKline Biologicals; ZOE-50 ClinicalTrials.gov number, NCT01165177.).
Topics: Adjuvants, Immunologic; Aged; Double-Blind Method; Female; Herpes Zoster; Herpes Zoster Vaccine; Humans; Injections, Intramuscular; Male; Middle Aged; Treatment Outcome; Vaccines, Subunit
PubMed: 25916341
DOI: 10.1056/NEJMoa1501184 -
Journal of Computational Biology : a... Apr 2015Identifying high-confidence candidate genes that are causative for disease phenotypes, from the large lists of variations produced by high-throughput genomics, can be...
Identifying high-confidence candidate genes that are causative for disease phenotypes, from the large lists of variations produced by high-throughput genomics, can be both time-consuming and costly. The development of novel computational approaches, utilizing existing biological knowledge for the prioritization of such candidate genes, can improve the efficiency and accuracy of the biomedical data analysis. It can also reduce the cost of such studies by avoiding experimental validations of irrelevant candidates. In this study, we address this challenge by proposing a novel gene prioritization approach that ranks promising candidate genes that are likely to be involved in a disease or phenotype under study. This algorithm is based on the modified conditional random field (CRF) model that simultaneously makes use of both gene annotations and gene interactions, while preserving their original representation. We validated our approach on two independent disease benchmark studies by ranking candidate genes using network and feature information. Our results showed both high area under the curve (AUC) value (0.86), and more importantly high partial AUC (pAUC) value (0.1296), and revealed higher accuracy and precision at the top predictions as compared with other well-performed gene prioritization tools, such as Endeavour (AUC-0.82, pAUC-0.083) and PINTA (AUC-0.76, pAUC-0.066). We were able to detect more target genes (9/18/19/27) on top positions (1/5/10/20) compared to Endeavour (3/11/14/23) and PINTA (6/10/13/18). To demonstrate its usability, we applied our method to a case study for the prediction of molecular mechanisms contributing to intellectual disability and autism. Our approach was able to correctly recover genes related to both disorders and provide suggestions for possible additional candidates based on their rankings and functional annotations.
Topics: Area Under Curve; Autism Spectrum Disorder; Gene Regulatory Networks; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Intellectual Disability; Models, Genetic; Molecular Sequence Annotation; Phenotype; ROC Curve
PubMed: 25844670
DOI: 10.1089/cmb.2015.0001 -
Transactions of the Royal Society of... Oct 2014The endemic treponemal diseases, consisting of yaws, bejel (endemic syphilis) and pinta, are non-venereal infections closely related to syphilis, and are recognized by...
The endemic treponemal diseases, consisting of yaws, bejel (endemic syphilis) and pinta, are non-venereal infections closely related to syphilis, and are recognized by WHO as neglected tropical diseases (NTDs). Despite previous worldwide eradication efforts the prevalence of yaws has rebounded in recent years and the disease is now a major public health problem in 14 countries. Adequate data on the epidemiology of bejel and pinta is lacking. Each disease is restricted to a specific ecological niche but all predominantly affect poor, rural communities. As with venereal syphilis, the clinical manifestations of the endemic treponemal diseases are variable and can be broken down in to early stage and late stage disease. Current diagnostic techniques are unable to distinguish the different causative species but newer molecular techniques are now making this possible. Penicillin has long been considered the mainstay of treatment for the endemic treponemal diseases but the recent discovery that azithromycin is effective in the treatment of yaws has renewed interest in these most neglected of the NTDs, and raised hopes that global eradication may finally be possible.
Topics: Anti-Bacterial Agents; Developing Countries; Endemic Diseases; Humans; Pinta; Syphilis; Yaws
PubMed: 25157125
DOI: 10.1093/trstmh/tru128 -
BMC Infectious Diseases Oct 2014More information is needed about time between sexual initiation and human papillomavirus (HPV) infection and development of cervical precancer.
Risk of first cervical HPV infection and pre-cancerous lesions after onset of sexual activity: analysis of women in the control arm of the randomized, controlled PATRICIA trial.
BACKGROUND
More information is needed about time between sexual initiation and human papillomavirus (HPV) infection and development of cervical precancer.
METHODS
The objectives were to investigate the time between first sexual activity and detection of first cervical HPV infection or development of first cervical intraepithelial neoplasia (CIN), and associated factors in women from the double-blind, multinational, 4-year PATRICIA trial. PATRICIA enroled women aged 15-25 years with no more than 6 lifetime sexual partners. Women were randomized 1:1 to the HPV-16/18 AS04-adjuvanted vaccine or to control, but only women from the control arm who began sexual intercourse during the study or within 6 months before enrolment, and had no HPV infection detected before the recorded date of their first sexual intercourse, were included in the present analysis. The time between onset of sexual activity and detection of the first cervical HPV infection or development of the first CIN lesion was analyzed using Kaplan-Meier and univariate and multivariable Cox proportional-hazards models.
RESULTS
A total of 9337 women were enroled in the control arm of PATRICIA of whom 982 fulfilled the required inclusion criteria for analysis. A cumulative total of 28%, 44%, and 62% of the subjects had HPV infection within 12, 24, and 48 months, respectively. The overall incidence rate was 27.08 per 100 person-years. The most common oncogenic types associated with 6-month persistent infection were HPV-16 (incidence rate: 2.74 per 100 person-years), HPV-51 (2.70), HPV-52 (1.66), HPV-66 (1.14), and HPV-18 (1.09). Increased infection risk was associated with more lifetime sexual partners, being single, Chlamydia trachomatis history, and duration of hormone use. CIN1+ and CIN2+ lesions were most commonly associated with HPV-16, with an overall incidence rate of 1.87 and 1.07 per 100 person-years, respectively. Previous cervical HPV infection was most strongly associated with CIN development.
CONCLUSIONS
More than 25% of women were infected with HPV within 1 year of beginning sexual activity. Without underestimating the value of vaccination at older ages, our findings emphasize its importance before sexual initiation.
TRIAL REGISTRATION
clinicaltrials.gov: NCT00122681 .
Topics: Adolescent; Adult; Aged, 80 and over; Female; Humans; Incidence; Papillomavirus Infections; Randomized Controlled Trials as Topic; Risk Factors; Sexual Behavior; Sexual Partners; Spain; Time Factors; Uterine Cervical Neoplasms; Young Adult; Uterine Cervical Dysplasia
PubMed: 25927224
DOI: 10.1186/s12879-014-0551-y