MD Conference Express ICAAC 2011 - (Page 4)

n F E A T U R E Infectious Disease Genomics: Individual Variability, New Opportunities Written by Rita Buckley Technological advances now enable comparisons of more than 500,000 genetic variants in subjects with disease and population controls. A large number of novel genetic loci that are involved in susceptibility to common immune-related diseases, such as rheumatoid arthritis and inflammatory bowel disease, have been identified through genomewide association studies (GWAS). More recently, this methodology has been successfully applied to identify loci that are involved in infectious disease susceptibility [Vannberg FO et al. Immunol Rev 2011]. David B. Goldstein, PhD, Duke University School of Medicine, Durham, North Carolina, USA, discussed recent studies, challenges, and next steps in infectious disease genomics. According to Dr. Goldstein, susceptibility to pathogens is a genetic trait, with heritability as high as the most heritable diseases. He emphasized that, so far as can be discerned, there are differences amongst people in their response to all known pathogens; citing findings from studies on the hepatitis C virus (HCV) as examples. Chronic infection with HCV affects 170 million people worldwide and is the leading cause of cirrhosis in North America. The recommended treatment involves a 48-week course of peginterferon-alpha-2b (PegIFN-alpha-2b) or alpha 2a (PegIFN-alpha-2a), combined with ribavirin (RBV)—an expensive process that is accompanied by significant adverse effects, (eg, anemia) that prevent some patients from completing treatment [Ge D et al. Nature 2009]. Many patients are not cured by treatment, and those with European ancestry have a significantly higher probability than patients of African descent of achieving sustained virological response (SVR) [Ge D et al. Nature 2009]. Response rates to pegIFN and RBV are also lower for Latino Americans and for those who are coinfected with HIV [RodriguezTorres M et al. N Engl J Med 2009]. East Asians, however, have higher SVR rates than patients of European ancestry [Yan KK et al. World J Gastroenterol 2008]. SVR Rates and rs12979860 on Chromosome 19 In a GWAS, Ge et al. [Nature 2009] reported that a genetic polymorphism on chromosome 19, rs1297860, was strongly associated with SVR in all patient groups, with the Caucasian population sample showing overwhelming genomewide significance (p=1.06 x 10-25) versus that seen in African-Americans (p=2.06 x 10-3). It is also known that the variants that are associated with SVR also influence natural clearance. In patients with HCV genotypes 2 or 3 (n=341) who were treated with 12 or 24 weeks of pegIFN/RBV therapy, rs12979860 determined the first phase of viral elimination (p<0.001). In patients who were treated for 24 weeks, rs1279860 also predicted the rate of SVR (p=0.02), especially in those with high baseline hepatitis C virus ribonucleic acid (HCV RNA levels (p=0.02) or aged >45 years (p=0.01). Patients who carried the CC genotype had higher baseline HCV RNA levels (p<0.001). When treated for 12 weeks, they did not achieve SVR more often than those who were carrying CT or TT genotypes. Peer-Reviewed Highlights from the 51st ICAAC 4 November 2011 www.mdconferencexpress.com http://www.mdconferencexpress.com http://www.icaac.org/ http://www.mdconferencexpress.com

Table of Contents for the Digital Edition of MD Conference Express ICAAC 2011

MD Conference Express ICAAC 2011
Contents
Infectious Disease Genomics
Emerging Resistance Among Gram-Negative Pathogens
Procalcitonin-Guided Antibiotic Therapy In Patients with Lower Respiratory Tract Infections
Combination Therapy with Flucytosine Improves Survival in AIDS-Related Cryptococcal Meningitis
CXA-201 Effective Against Common ICU Pathogens
Tigecycline Plus Standard Therapy Is More Effective For Treating Infections in Febrile Neutropenic Cancer Patients
Interventions Aimed at Reducing MRSA BSIs Led to Decreased Rates of Nosocomial MSSA BSIs
Is the Effectiveness of aP Vaccine in Pre-Adolescents Insufficient?
TMC435 Effective in the Treatment of HCV Genotype 1 Infection
HIV
Vaccines
Antibiotic Resistance
Drug Discovery
The Conundrum of MDR TB and Combination Therapy
New Drugs to Treat MDR Pathogens
Immunizations in Reproductive Health
Why Can’t Microbes Just Get Along?
The Role of Adjunctive Steroids in the Treatment of Bacterial Meningitis
Human and Animal Viruses Share “One World” and Emerging Zoonotic Infections Continue to Threaten

MD Conference Express ICAAC 2011

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