Chikungunya Virus Transmission Found in the United States

It’s official: the chikungunya virus has arrived in the United States. Public health authorities confirmed the first 2 cases of local transmission in Florida about 6 weeks ago. This event was not unexpected, said health authorities. In December 2013, the World Health Organization reported the first local transmission of chikungunya virus in the Western Hemisphere, in the Caribbean. Within months, the disease spread through much of the Caribbean and Central and South America. As of late July, the Pan American Health Organization was reporting the number of suspected cases had topped 400 000 and was rapidly increasing. In French Saint Martin, where the virus first began spreading, an estimated 12% of the population has been infected, according to J. Erin Staples, MD, PhD, medical epidemiologist with the US Centers for Disease Control and Prevention (CDC) division of vector-borne diseases in Fort Collins, Colorado. Reflecting this spread, the number of US travelers who became infected with the virus during travel to the regions also has rapidly climbed (read more)

Ebola virus outbreak in Africa

Levels of exposure
Number of people that might require treatment (source)
Map and graph showing cases by week

RUO real-time PCR protocols without nucleic acid purification

for DNA viruses : AmpDirect (Shimadzu/Nacalai); HSV (ref), HBV (ref)

for RNA viruses : Cells-to-CT(TM) 1-Step Power SYBR(R) Green Kit (Life Technologies)

Since haemolysed, lipaemic and icteric serum samples from patients are inevitable in clinical practice, investigators should evaluate the interference of these endogenous substances (also known as the serum index), including conjugated bilirubin, haemoglobin and triglycerides, in real-time PCR.
Avoiding DNA extraction reduces risk of cross contamination, carryover and/or procedural error.

Treatment of Hepatitis C A Systematic Review

Importance : Hepatitis C virus (HCV) infects more than 185 million individuals worldwide. Twenty percent of patients chronically infected with HCV progress to cirrhosis. New, simpler therapeutics using direct-acting antivirals that target various stages of the HCV life cycle are in development to eradicate HCV without concomitant interferon.
Objectives : To summarize published evidence on safety, efficacy (measured by a sustained virologic response [SVR], which is the treatment goal of undetectable plasma HCV RNA 12 or 24 weeks after therapy completion), and tolerability of current US Food and Drug Administration–approved interferon-based regimens and oral interferon-free regimens used for treating HCV infection and coinfection with human immunodeficiency virus (HIV) and HCV; to provide treatment recommendations for specialists and generalists based on published evidence.
Evidence Review : A literature search of Web of Science, Scopus, Embase, Agricola, Cochrane Library, Cinahl Plus, ClinicalTrials.gov, Conference Papers Index, Gideon, PsycINFO, Google Scholar, and Oaister was conducted from January 1, 2009, to May 30, 2014. Publications describing phase 2, 3, and 4 studies evaluating the treatment of HCV were included. Forty-one studies involving 19 063 adult patients were included. Strength of clinical data and subsequent HCV treatment recommendations were graded according to the Oxford Centre for Evidence-Based Medicine.
Findings : Patients infected with HCV genotype 1 represent 60% to 75% of HCV infections in the United States. Hepatitis C virus genotype 1 is more difficult to cure than genotype 2 or genotype 3. Patients with HCV genotype 1 should receive treatment with sofosbuvir + pegylated interferon + ribavirin because of the shorter duration of therapy and high rates of SVR (89%-90%). Simeprevir + pegylated interferon + ribavirin is an alternative for patients with HCV genotype 1 (SVR, 79%-86%). Patients with HCV genotypes 2 and 3, representing 20% to 29% of US HCV infections, should receive therapy with sofosbuvir + ribavirin alone (SVR for genotype 2, 12 weeks’ duration: 82%-93%; SVR for genotype 3, 24 weeks’ duration, 80%-95%). Patients with HIV-HCV coinfection and patients with compensated cirrhosis (ie, cirrhosis but preserved synthetic liver function) should receive the same treatment as HCV-monoinfected patients.
Conclusions and Relevance : New, short-duration, simpler therapies result in high SVR rates for HCV-infected patients. In conjunction with increased screening for HCV as suggested by recent Centers for Disease Control and Prevention guidelines, availability of new therapies may lead to the treatment of many more people with chronic HCV infection (read more)

Distribution of rotavirus strains and strain-specific effectiveness of the rotavirus vaccine after its introduction: a systematic review and meta-analysis

Background : Concerns exist about whether monovalent (RV1) and pentavalent (RV5) rotavirus vaccines provide adequate protection against diverse strains and whether vaccine introduction will lead to selective pressure. We aimed to investigate the distribution of rotavirus strains and strain-specific rotavirus vaccine effectiveness after vaccine introduction.
Methods : We did a systematic review of published work to assess the strain-specific effectiveness of RV1 and RV5 rotavirus vaccines. We classified strains as homotypic, partly heterotypic, and fully heterotypic based on the amount of antigen-matching between strain and vaccine. When studies reported vaccine effectiveness against single antigens (G-type or P-type), we categorised them as either single-antigen vaccine type or single-antigen non-vaccine type. Our primary outcome was strain-specific vaccine effectiveness, comparing effectiveness of homotypic strains with fully or partly heterotypic strains. A secondary outcome was the prevalence of rotavirus strains after vaccine introduction. We estimated pooled odds ratios using random-effect regression models, stratified by country income level and vaccine type, and tested for differences in strain-specific vaccine effectiveness. We assessed strain distribution trends from surveillance reports.
Findings : In high-income countries, RV1 pooled vaccine effectiveness was 94% (95% CI 80—98) against homotypic strains, 71% (39—86) against partly heterotypic strains, and 87% (76—93) against fully heterotypic strains. In middle-income settings, respective pooled data were 59% (36—73), 72% (58—81), and 47% (28—61). In high-income countries, RV5 vaccine effectiveness was 83% (78—87) against homotypic strains, 82% (70—89) against single-antigen vaccine type strains, 82% (70—89) against partly heterotypic strains, and 75% (47—88) against single-antigen non-vaccine type strains. In middle-income settings, RV5 vaccine effectiveness was 70% (58—78) against single-antigen vaccine type strains, 37% (10—56) against partly heterotypic strains, and 87% (38—97) against single-antigen non-vaccine type strains. No difference was noted in vaccine effectiveness for either RV1 or RV5 in any setting (all p>0·05). Prevalent strains in countries using RV1 were G2P[4] (2198 of 4428, 50%) and G1P[8] (953, 22%), and those in countries using RV5 were G1P[8] (1280 of 3875, 33%) and G2P[4] (1169, 30%). Sustained predominance of a single strain was not recorded.
Interpretation : RV1 and RV5 exert similar effectiveness against homotypic and heterotypic rotavirus strains. Persistence of specific strains was not recorded, suggesting vaccine-induced selective pressure did not occur. Expansion of rotavirus surveillance efforts to low-income countries and ongoing surveillance are crucial to identify emergence of new strains and to assess strain-specific vaccine effectiveness in various settings (read more)

Host Species Restriction of Middle East Respiratory Syndrome Coronavirus through Its Receptor, Dipeptidyl Peptidase 4

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and ferret cells enabled MERS-CoV replication, whereas expression of hamster or ferret DPP4 did not. Modeling the binding energies of MERS-CoV spike protein RBD to DPP4 of human (susceptible) or hamster (nonsusceptible) identified five amino acid residues involved in the DPP4-RBD interaction. Expression of hamster DPP4 containing the five human DPP4 amino acids rendered BHK cells susceptible to MERS-CoV, whereas expression of human DPP4 containing the five hamster DPP4 amino acids did not. Using the same approach, the potential of MERS-CoV to utilize the DPP4s of common Middle Eastern livestock was investigated. Modeling of the DPP4 and MERS-CoV RBD interaction predicted the ability of MERS-CoV to bind the DPP4s of camel, goat, cow, and sheep. Expression of the DPP4s of these species on BHK cells supported MERS-CoV replication. This suggests, together with the abundant DPP4 presence in the respiratory tract, that these species might be able to function as a MERS-CoV intermediate reservoir (read more)

Defective Viral Genomes: Critical Danger Signals of Viral Infections

Viruses efficiently block the host antiviral response in order to replicate and spread before host intervention. The mechanism initiating antiviral immunity during stealth viral replication is unknown, but recent data demonstrate that defective viral genomes generated at peak virus replication are critical for this process in vivo. This article summarizes the supporting evidence and highlights gaps in our understanding of the mechanisms and impact of immunostimulatory defective viral genomes generated during natural infections (read more)