domenica 28 dicembre 2014

Vaccinated Populations Can Get Flu

The US Navy has a mandatory influenza vaccination policy, but even a high immunization rate couldn’t prevent a shipboard influenza outbreak in February 2014. Nearly one-quarter of the 102 crew members on a minesweeper moored in San Diego for 2 months developed symptoms attributed to influenza A(H3N2) virus, even though 99% of the affected men had been vaccinated (read more)

mercoledì 12 novembre 2014

Treating Progressive Multifocal Leukoencephalopathy With Interleukin 7 and Vaccination With JC Virus Capsid Protein VP1

Progressive multifocal leukoencephalopathy is a currently untreatable infection of the brain. Here, we demonstrate in 2 patients that treatment with interleukin 7, JC polyomavirus (JCV) capsid protein VP1, and a Toll-like receptor 7 agonist used as adjuvant, was well tolerated, and showed a very favorable safety profile and unexpected efficacy that warrant further investigation (read more)

sabato 8 novembre 2014

Ebola virus convalescent blood products: Where we are now and where we may need to go

The world is regularly exposed to emerging infections with the potential to burst into a pandemic. One possible way to treat patients, when no other treatment is yet developed, is passive immunization performed by transfusing blood, plasma or plasma immunoglobulin fractions obtained from convalescent donors who have recovered from the disease and have developed protective antibodies. The most recent on-going epidemic is caused by the Ebola virus, a filovirus responsible for Ebola virus disease, a severe, often lethal, hemorrhagic fever. Recently, the use of convalescent blood products was proposed by the WHO as one early option for treating patients with Ebola virus disease. This publication provides an overview of the various convalescent blood products and technological options that could theoretically be considered when there is a need to rely on this therapeutic approach. In countries without access to advanced blood-processing technologies, the choice may initially be restricted to convalescent whole blood or plasma. In technologically advanced countries, additional options for convalescent blood products are available, including virally inactivated plasma and fractionated immunoglobulins. The preparation of minipool immunoglobulins is also a realistic option to consider (read more)

giovedì 6 novembre 2014

Central nervous system alterations caused by infection with the human respiratory syncytial virus

Worldwide, the human respiratory syncytial virus (hRSV) is the leading cause of infant hospitalization because of acute respiratory tract infections, including severe bronchiolitis and pneumonia. Despite intense research, to date there is neither vaccine nor treatment available to control hRSV disease burden globally. After infection, an incubation period of 3–5 days is usually followed by symptoms, such as cough and low-grade fever. However, hRSV infection can also produce a larger variety of symptoms, some of which relate to the individual's age at infection. Indeed, infants can display severe symptoms, such as dyspnea and chest wall retractions. Upon examination, crackles and wheezes are also common features that suggest infection by hRSV. Additionally, infection in infants younger than 1 year is associated with several non-specific symptoms, such as failure to thrive, periodic breathing or apnea, and feeding difficulties that usually require hospitalization. Recently, neurological symptoms have also been associated with hRSV respiratory infection and include seizures, central apnea, lethargy, feeding or swallowing difficulties, abnormalities in muscle tone, strabismus, abnormalities in the CSF, and encephalopathy. Here, we discuss recent findings linking the neurological, extrapulmonary effects of hRSV with infection and functional impairment of the CNS (read more)

martedì 9 settembre 2014

In Vivo Reactivation of Latent Herpes Simplex Virus 1 in Mice Can Occur in the Brain before Occurring in the Trigeminal Ganglion

Herpes simplex virus 1 (HSV-1) establishes latency in neurons of the brains and sensory ganglia of humans and experimentally infected mice. The latent virus can reactivate to cause recurrent infection. Both primary and recurrent infections can induce diseases, such as encephalitis. In humans, the majority of encephalitis cases occur as a recurrent infection. However, in the past, numerous mouse studies documented that viral reactivation occurs efficiently in the ganglion, but extremely rarely in the brain, when assessed ex vivo by cultivating minced tissue explants. Here, we compare the brains and the trigeminal ganglia of mice latently infected with HSV-1 (strain 294.1 or McKrae) for levels of viral genomes and in vivo reactivation. The numbers of copies of 294.1 and McKrae genomes in the brain stem were significantly greater than those in the trigeminal ganglion. Most importantly, 294.1 and McKrae reactivation was detected in the brain stems earlier than in the trigeminal ganglia of mice treated with hyperthermia to reactivate latent virus in vivo. In addition, the brain stem yielded reactivated virus at a high frequency compared with the trigeminal ganglion, especially in mice latently infected with 294.1 after hyperthermia treatment. These results provide evidence that recurrent brain infection can be induced by the reactivation of latent virus in the brain in situ.
IMPORTANCE Herpes simplex virus 1 (HSV-1) establishes latency in neurons of the brains and sensory ganglia of humans and experimentally infected mice. The latent virus can reactivate to cause recurrent infection. In the past, studies of viral reactivation focused on the ganglion, because efficient viral reactivation was detected in the ganglion but not in the brain when assessed ex vivo by cultivating mouse tissue explants. In this study, we report that the brain contains more viral genomes than the trigeminal ganglion in latently infected mice. Notably, the brain yields reactivated virus early and efficiently compared with the trigeminal ganglion after mice are stimulated to reactivate latent virus. Our findings raise the potential importance of HSV-1 latent infection and reactivation in the brain (read more)

giovedì 28 agosto 2014

Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak

In memory of the co-authors Mohamed Fullah, Mbalu Fonnie, Alex Moigboi, Alice Kovoma, and S. Humarr Khan, working at the Kenema Government Hospital, Kenema, Sierra Leone, who died from Ebola before the report got published in Science :

In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2,000x coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from Middle African lineages ~2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Since many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response (read more).

Robustness against serum neutralization of a poliovirus type 1 from a lethal epidemic of poliomyelitis in the Republic of Congo in 2010

In 2010, a large outbreak of poliomyelitis with unusual 47% lethality occurred in Pointe Noire, Republic of Congo. Vaccine-mediated immunity against the outbreak virus was never investigated. A wild poliovirus 1 (WPV1) isolated from a fatal case (termed PV1-RC2010) showed a previously unknown combination of amino acid exchanges in critical antigenic site 2 (AgS2, VP1 capsid protein positions 221SAAL→221PADL). These exchanges were also detected in an additional 11 WPV1 strains from fatal cases. PV1-RC2010 escaped neutralization by three different mAbs relevant for AgS2. Virus neutralization was tested in sera from fatal cases, who died before supplementary immunization (n = 24), Gabonese recipients of recent oral polio vaccination (n = 12), routinely vaccinated German medical students (n = 34), and German outpatients tested for antipoliovirus immunity (n = 17) on Vero, human rhabdomyosarcoma, and human epidermoid carcinoma 2 cells. Fatal poliomyelitis cases gave laboratory evidence of previous trivalent vaccination. Neutralizing antibody titers against PV1-RC2010 were significantly lower than those against the vaccine strain Sabin-1, two genetically distinct WPV1s isolated in 1965 and 2010 and two genetically distinct vaccine-derived PV strains. Of German vaccinees tested according to World Health Organization protocols, 15-29% were unprotected according to their neutralization titers (<1:8 serum dilution), even though all were protected against Sabin-1. Phylogenetic analysis of the WPV1 outbreak strains suggested a recent introduction of virus progenitors from Asia with formation of separate Angolan and Congolese lineages. Only the latter carried both critical AgS2 mutations. Antigenetically variant PVs may become relevant during the final phase of poliomyelitis eradication in populations with predominantly vaccine-derived immunity. Sustained vaccination coverage and clinical and environmental surveillance will be necessary (read more)

mercoledì 27 agosto 2014

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)

sabato 16 agosto 2014

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.

mercoledì 13 agosto 2014

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,, 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)

martedì 29 luglio 2014

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)

giovedì 24 luglio 2014

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)

Receptor binding by H10 influenza viruses

H10N8 follows H7N9 and H5N1 as the latest in a line of avian influenza viruses that cause serious disease in humans and have become a threat to public health. Since December 2013, three human cases of H10N8 infection have been reported, two of whom are known to have died. To gather evidence relating to the epidemic potential of H10 we have determined the structure of the haemagglutinin of a previously isolated avian H10 virus and we present here results relating especially to its receptor-binding properties, as these are likely to be major determinants of virus transmissibility. Our results show, first, that the H10 virus possesses high avidity for human receptors and second, from the crystal structure of the complex formed by avian H10 haemagglutinin with human receptor, it is clear that the conformation of the bound receptor has characteristics of both the 1918 H1N1 pandemic virus and the human H7 viruses isolated from patients in 2013 (ref. 3). We conclude that avian H10N8 virus has sufficient avidity for human receptors to account for its infection of humans but that its preference for avian receptors should make avian-receptor-rich human airway mucins an effective block to widespread infection. In terms of surveillance, particular attention will be paid to the detection of mutations in the receptor-binding site of the H10 haemagglutinin that decrease its avidity for avian receptor, and could enable it to be more readily transmitted between humans (read more)

martedì 22 luglio 2014

Helminth infection reactivates latent gamma-herpervirus via cytokine competition at a viral promoter

Mammals are co-infected by multiple pathogens that interact through unknown mechanisms. We found that helminth infection, characterized by the induction of the cytokine interleukin-4 (IL-4) and the activation of the transcription factor Stat6, reactivated murine gammaherpesvirus infection in vivo. IL-4 promoted viral replication and blocked the antiviral effects of interferon-γ (IFNγ) by inducing Stat6 binding to the promoter for an important viral transcriptional transactivator. IL-4 also reactivated human Kaposi's sarcoma associated herpesvirus from latency in cultured cells. Exogenous IL-4 plus blockade of IFNγ reactivated latent murine gammaherpesvirus infection in vivo, suggesting a "two-signal" model for viral reactivation. Thus chronic herpesvirus infection, a component of the mammalian virome, is regulated by the counterpoised actions of multiple cytokines on viral promoters that have evolved to sense host immune status (read more)

martedì 15 luglio 2014

Smallpox Lives to Die Another Day

The decision about whether and when to destroy the last living samples of the Variola virus, which causes smallpox, was postponed when the topic came up on the agenda at the World Health Organization’s (WHO’s) annual World Health Assembly in Geneva, Switzerland, in May. After the WHO declared smallpox to be eradicated in 1980, scientists have continued to debate whether to destroy the 2 remaining stocks of the virus, which are contained in laboratories in the Russian State Research Center of Virology and Biotechnology in Koltsovo and at the US Centers for Disease Control and Prevention in Atlanta, Georgia. The issue was last discussed at the World Health Assembly in 2011, when it was decided that the stocks should be destroyed, but discussion of when was deferred until this year’s meeting (read more)

mercoledì 9 luglio 2014

Human papillomavirus prevalence in oropharyngeal cancer before vaccine introduction, United States.

We conducted a study to determine prevalence of HPV types in oropharyngeal cancers in the United States and establish a prevaccine baseline for monitoring the impact of vaccination. HPV DNA was extracted from tumor tissue samples from patients in whom cancer was diagnosed during 1995-2005. The samples were obtained from cancer registries and Residual Tissue Repository Program sites in the United States. HPV was detected and typed by using PCR reverse line blot assays. Among 557 invasive oropharyngeal squamous cell carcinomas, 72% were positive for HPV and 62% for vaccine types HPV16 or 18. Prevalence of HPV-16/18 was lower in women (53%) than in men (66%), and lower in non-Hispanic Black patients (31%) than in other racial/ethnic groups (68%-80%). Results indicate that vaccines could prevent most oropharyngeal cancers in the United States, but their effect may vary by demographic variables (read more)

NIH finds forgotten smallpox store

Smallpox, officially preserved in two repositories worldwide, may have been sitting alive and well in an unsecured US government refrigerator. On 8 July, the US Centers for Disease Control (CDC) announced that vials containing the deadly virus had been discovered in a cardboard box in the refrigerator, located on the National Institutes of Health (NIH) campus in Bethesda, Maryland. That refrigerator belongs to the US Food and Drug Administration (FDA), which has conducted some of its research at the Bethesda site since 1972. On 1 July, FDA researchers discovered the vials — labelled "variola," the name of the virus that causes smallpox — while conducting an inventory of the lab in preparation for a move to FDA's headquarters in White Oak, Maryland. NIH safety officials determined that the virus had not leaked and there was no danger to the employees who had found it, and then sequestered the samples in a secure lab on campus, the agency said (read more)

mercoledì 2 luglio 2014

Evolution of Norovirus

Norovirus (NoV) is now the dominant aetiological agent of acute gastroenteritis and with the recent introduction of rotavirus vaccines in many countries, this is likely to remain the case. NoV, has a significant impact on human well-being in terms of morbidity, economic costs and mortality in developing countries. NoVs are divided into six genogroups (GI–GVI), but only GI, GII and GIV are known to infect humans, with GII being the most prevalent causing over 95% of human infections. The immune system is thought to drive selection of emerging pandemic NoVs through both antigenic drift and shift. This phenomenon results in replacement of dominant circulating viruses approximately every 3 years, with new variants able to re-infect hosts previously infected with earlier viruses. This review explores the evolutionary aspects of contemporary NoVs (read more)

Review: Laboratory diagnosis and surveillance of Creutzfeldt–Jakob disease

Creutzfeldt–Jakob disease (CJD) is a representative human transmissible spongiform encephalopathy associated with central nervous system degeneration. Prions, the causative agents of CJD, are composed of misfolded prion proteins and are able to self-replicate. While CJD is a rare disease affecting only 1–1.5 people per million worldwide annually, it has attracted both scientific and public attention as a threatening disease since an epidemic of variant CJD (vCJD) cases appeared in the mid-1990s. Due to its unconventional transmission and invariable fatality, CJD poses a serious risk to public health. The hundreds of sporadic, genetic, and iatrogenic CJD cases as well as potential zoonotic transmission suggest that CJD is an ongoing concern for the field of medicine. Nevertheless, treatment aimed at clinical prevention and treatment that reverses the course of disease does not exist currently. Active surveillance and effective laboratory diagnosis of CJD are, therefore, critical. In this report, the surveillance systems and laboratory tests used currently to diagnose CJD in different countries are reviewed. The current efforts to improve surveillance and diagnosis for CJD using molecular and biochemical findings are also described (read more)

sabato 28 giugno 2014

Polio will go, acute flaccid paralysis will stay

The Global Polio Eradication Initiative has made tremendous progress since its launch by WHO in 1988, reducing polio cases from an estimated 350 000 in 1988 to about 407 in 2013. The number of countries that have never interrupted wild poliovirus transmission decreased from more than 125 to only three countries (Nigeria, Afghanistan, and Pakistan). In 1999, the eradication of wild poliovirus type 2 was achieved. The last case of poliovirus type 3 occurred on Nov 10, 2012, in Nigeria. The remaining goal of the Global Polio Eradication Initiative is to stop the transmission of all wild poliovirus and vaccine-derived poliovirus through supplementary immunisation activities, and environmental and acute flaccid paralysis surveillance (read more)

West Nile virus nucleic acid persistence in whole blood months after clearance in plasma: implication for transfusion and transplantation safety

Background : Previous reports of West Nile virus (WNV) RNA persistence in blood compartments have raised concerns around the remaining risk of WNV transfusion transmission. This study characterized the dynamics of WNV viremia in blood compartments in a longitudinal cohort of 54 WNV-infected blood donors.
Study Design and Methods : Blood samples were collected throughout the year after WNV RNA–positive blood donation (index) and characterized for WNV immunoglobulin (Ig)M and IgG antibodies and for WNV RNA by real-time reverse transcription–polymerase chain reaction. WNV viral loads were compared in plasma and whole blood samples and correlated with blood groups and clinical outcomes.
Results : WNV RNA persisted in the red blood cell (RBC) compartment up to 3 months postindex in 42% of the donors. Donors with the highest WNV RNA levels in plasma at index maintained the highest WNV RNA levels in whole blood over the 3 months postindex. Blood group A donors maintained higher postindex WNV viral load in whole blood than blood group O individuals (p = 0.027). Despite a trend for WNV RNA to persist longer in whole blood from symptomatic subjects, no significant association was found between WNV RNA levels in whole blood and disease outcome.
Conclusion : This study confirmed that WNV RNA persists in the RBC fraction in whole blood and further suggested that the level of persistence in whole blood may be a reflection of initial viral burden in plasma. The association with blood groups suggests that WNV adherence to RBCs may be mediated by molecules overrepresented at the surface of blood group A RBCs (read more).

lunedì 23 giugno 2014

Team science and the creation of a novel rotavirus vaccine in India: a new framework for vaccine development

In The Lancet, findings from Nita Bhandari and colleagues' phase 3 clinical trial show the safety and efficacy of the 116E rotavirus vaccine against severe rotavirus gastroenteritis in Indian infants. The vaccine has an efficacy similar to that of two licensed oral rotavirus vaccines—RotaTeq (Merck) and Rotarix (GlaxoSmithKline)—when tested in low-income settings. However, the timeline of development has been unique and unconventional. The vaccine was not the product of a major multinational manufacturer, but rather, the result of work by team science, based in India (read more)

sabato 21 giugno 2014

Preclinical Detection of Variant CJD and BSE Prions in Blood

The emergence of variant Creutzfeldt Jakob Disease (vCJD) is considered a likely consequence of human dietary exposure to Bovine Spongiform Encephalopathy (BSE) agent. More recently, secondary vCJD cases were identified in patients transfused with blood products prepared from apparently healthy donors who later went on to develop the disease. As there is no validated assay for detection of vCJD/BSE infected individuals the prevalence of the disease in the population remains uncertain. In that context, the risk of vCJD blood borne transmission is considered as a serious concern by health authorities. In this study, appropriate conditions and substrates for highly efficient and specific in vitro amplification of vCJD/BSE agent using Protein Misfolding Cyclic Amplification (PMCA) were first identified. This showed that whatever the origin (species) of the vCJD/BSE agent, the ovine Q171 PrP substrates provided the best amplification performances. These results indicate that the homology of PrP amino-acid sequence between the seed and the substrate is not the crucial determinant of the vCJD agent propagation in vitro. The ability of this method to detect endogenous vCJD/BSE agent in the blood was then defined. In both sheep and primate models of the disease, the assay enabled the identification of infected individuals in the early preclinical stage of the incubation period. Finally, sample panels that included buffy coat from vCJD affected patients and healthy controls were tested blind. The assay identified three out of the four tested vCJD affected patients and no false positive was observed in 141 healthy controls. The negative results observed in one of the tested vCJD cases concurs with results reported by others using a different vCJD agent blood detection assay and raises the question of the potential absence of prionemia in certain patients (read more)

Replication of Many Human Viruses Is Refractory to Inhibition by Endogenous Cellular MicroRNAs

The issue of whether viruses are subject to restriction by endogenous microRNAs (miRNAs) and/or by virus-induced small interfering RNAs (siRNAs) in infected human somatic cells has been controversial. Here, we address this question in two ways. First, using deep sequencing, we demonstrate that infection of human cells by the RNA virus dengue virus (DENV) or West Nile virus (WNV) does not result in the production of any virus-derived siRNAs or viral miRNAs. Second, to more globally assess the potential of small regulatory RNAs to inhibit virus replication, we used gene editing to derive human cell lines that lack a functional Dicer enzyme and that therefore are unable to produce miRNAs or siRNAs. Infection of these cells with a wide range of viruses, including DENV, WNV, yellow fever virus, Sindbis virus, Venezuelan equine encephalitis virus, measles virus, influenza A virus, reovirus, vesicular stomatitis virus, human immunodeficiency virus type 1, or herpes simplex virus 1 (HSV-1), failed to reveal any enhancement in the replication of any of these viruses, although HSV-1, which encodes at least eight Dicer-dependent viral miRNAs, did replicate somewhat more slowly in the absence of Dicer. We conclude that most, and perhaps all, human viruses have evolved to be resistant to inhibition by endogenous human miRNAs during productive replication and that dependence on a cellular miRNA, as seen with hepatitis C virus, is rare. How viruses have evolved to avoid inhibition by endogenous cellular miRNAs, which are generally highly conserved during metazoan evolution, remains to be determined.
IMPORTANCE Eukaryotic cells express a wide range of small regulatory RNAs, including miRNAs, that have the potential to inhibit the expression of mRNAs that show sequence complementarity. Indeed, previous work has suggested that endogenous miRNAs have the potential to inhibit viral gene expression and replication. Here, we demonstrate that the replication of a wide range of pathogenic viruses is not enhanced in human cells engineered to be unable to produce miRNAs, indicating that viruses have evolved to be resistant to inhibition by miRNAs. This result is important, as it implies that manipulation of miRNA levels is not likely to prove useful in inhibiting virus replication. It also focuses attention on the question of how viruses have evolved to resist inhibition by miRNAs and whether virus mutants that have lost this resistance might prove useful, for example, in the development of attenuated virus vaccines (read more)

martedì 3 giugno 2014

The Human Fetal Glial Cell Line SVG p12 Contains Infectious BK Polyomavirus

The human fetal glial cell line SVG was generated in 1985 by transfecting primary fetal brain cells with a plasmid containing an origin-defective mutant of simian virus 40 (SV40). The cells, which express SV40 large T-antigen, support the replication of human JC polyomavirus (JCPyV) and have been used for JCPyV studies but also for other studies in which cells of neural origin were desirable. We intended to use the SVG p12 cells from ATCC for antiviral drug studies with JCPyV. However, during initial experiments, immunofluorescence microscopy controls unexpectedly revealed cells expressing the late viral proteins VP1, VP2/VP3, and agno. This was confirmed by Western blotting. Since our agnoprotein antiserum is specific for BKPyV agnoprotein, infection with BKPyV was suspected. Indeed, specific BKPyV PCR of SVG p12 supernatants revealed a viral load of >1 × 1010 genomic equivalents/ml. Negative-staining electron microscopy showed characteristic polyomavirus virions, and infectious BKPyV was transmitted from SVG p12 supernatant to other cells. Long-range PCR covering the viral genome, followed by DNA sequencing, identified BKPyV strain UT as well as deletion derivatives. This was confirmed by next-generation sequencing. JCPyV (MAD-4) was found to infect apparently uninfected and BKPyV-infected SVG p12 cells. In total, 4 vials from 2 different ATCC lots of SVG p12 cells dating back to 2006 contained BKPyV, whereas the subclone SVG-A was negative. In conclusion, SVG p12 cells from ATCC contain infectious BKPyV. This may have affected results and interpretations of previous studies, and caution should be taken in future experiments (read more)

Polio eradication: the CIA and their unintended victims

On May 2, 2011, President Barack Obama announced that the US Central Intelligence Agency (CIA) had located and killed Osama Bin Laden. The agency organised a fake hepatitis vaccination campaign in Abottabad, Pakistan, in a bid to obtain DNA from the children of Bin Laden, to confirm the presence of the family in a compound and sanction the rollout of a risky and extensive operation. Release of this information has had a disastrous effect on worldwide eradication of infectious diseases, especially polio.
On May 16, 2014, the White House announced that the CIA will no longer use vaccination programmes as a cover for espionage. The news comes in the wake of a series of militant attacks on polio vaccination workers in Pakistan, with legitimate health-care workers targeted as being US spies. The attacks have forced organisations such as the UN to suspend polio vaccination efforts in Pakistan, and have severely hampered anti-polio efforts, with parents refusing to have their children vaccinated. News of the vaccination programme led to a banning of vaccination in areas controlled by the Pakistan Taliban, and added to existing scepticism surrounding the sincerity of public health efforts by the international health community.
Consequently, WHO declared that polio has re-emerged as a public health emergency in Pakistan—one of only three countries, including Afghanistan and Nigeria, where the disease remains endemic. According to the Global Polio Eradication Initiative, 61 of 77 cases of polio reported this year have been in Pakistan, and cases of paralytic polio have spiked, with 66 cases reported up to now, compared with only 14 last year.
The lesson learned from the experience in Pakistan is that public health programmes should be politically neutral. Although the announcement from the White House might go some way to building bridges towards that neutrality, health officials and local leaders now have the challenge of convincing communities that vaccination is not merely beneficial, but vital for children (read more)

[Review] Infectious causes of stroke

Most infectious pathogens have anecdotal evidence to support a link with stroke, but certain pathogens have more robust associations, in which causation is probable. Few dedicated prospective studies of stroke in the setting of infection have been done. The use of head imaging, a clinical standard of diagnostic care, to confirm stroke and stroke type is not universal. Data for stroke are scarce in locations where infections are probably most common, making it difficult to reach conclusions on how populations differ in terms of risk of infectious stroke (read more)

sabato 24 maggio 2014

Low-Cost Mobile Phone Microscopy with a Reversed Mobile Phone Camera Lens

The increasing capabilities and ubiquity of mobile phones and their associated digital cameras offer the possibility of extending low-cost, portable diagnostic microscopy to underserved and low-resource areas. However, mobile phone microscopes created by adding magnifying optics to the phone's camera module have been unable to make use of the full image sensor due to the specialized design of the embedded camera lens, exacerbating the tradeoff between resolution and field of view inherent to optical systems. This tradeoff is acutely felt for diagnostic applications, where the speed and cost of image-based diagnosis is related to the area of the sample that can be viewed at sufficient resolution. Here we present a simple and low-cost approach to mobile phone microscopy that uses a reversed mobile phone camera lens added to an intact mobile phone to enable high quality imaging over a significantly larger field of view than standard microscopy. We demonstrate use of the reversed lens mobile phone microscope to identify red and white blood cells in blood smears and soil-transmitted helminth eggs in stool samples (read more)

Herpes Zoster Involving the S1 Dermatome

A 19-month-old female infant presented with a 1-week history of ascending linear erythematous eruptions on the left calf. She showed no indications of immune disturbances and was a full-term infant with a healthy rate of weight gain and development. She had been immunized with the varicella vaccine 7 months before presentation. Physical examination revealed a vesicular rash in the S1 dermatome of the left leg (Panel A). A scraping from the base of several vesicles was obtained, and a direct immunofluorescence antigen assay was performed; the results were positive for the varicella–zoster virus (read more)

sabato 17 maggio 2014

Movement of Chikungunya Virus into the Western Hemisphere

Chikungunya virus (CHIKV) is an alphavirus transmitted in an urban epidemic cycle by the mosquitoes Aedes aegypti andAe. albopictus. CHIKV outbreaks are characterized by rapid spread and infection rates as high as 75%; 72%–93% of infected persons become symptomatic. The disease manifests as acute fever and potentially debilitating polyarthralgia. In a variable proportion of cases, polyarthritis and fatigue can persist for 2 years or longer. During outbreaks, the large percentage of symptomatic infections places a considerable strain on resources of local health care providers and hospitals. Fortunately, death from chikungunya is rare (read more)

giovedì 8 maggio 2014

Antibodies for Middle East virus

Two independent teams have identified antibodies that can vanquish a deadly virus first reported in the Middle East. Since it appeared in 2012, the Middle East respiratory syndrome (MERS) coronavirus has caused disease in at least 261 people and killed nearly 100 in Asia, North Africa and Europe as of 26 April 2014 (read more)

Taming the Transplantation Troll by Targeting Terminase

The immunosuppressive drugs required after stem-cell transplantation render patients susceptible to opportunistic infections. The most important of these infections, in terms of both abundance and severity, is cytomegalovirus (CMV), which has been dubbed the “troll of transplantation.” Fortunately, the clinical effects of CMV infection have been reduced by preemptive therapy. Levels of CMV DNA in the blood (viremia) are monitored with the use of polymerase-chain-reaction (PCR) assays and, if viremia is detected, patients receive ganciclovir (or its prodrug valganciclovir) until viral DNA is no longer detectable (read more)

Ebola — A Growing Threat?

The recent emergence of Zaire ebolavirus in West Africa1 has come as a surprise in a region more commonly known for its endemic Lassa fever, another viral hemorrhagic fever caused by an Old World arenavirus. Yet the region has seen previous ebolavirus activity. In the mid-1990s, scientists discovered Côte d'Ivoire ebolavirus (now known as Taï Forest ebolavirus) as a cause of a single reported nonfatal case in a researcher who performed a necropsy on an infected chimpanzee. The episode initiated a major research investigation in and around the Taï Forest region — an effort that failed to identify the reservoir of this new Ebola species. Since that incident, West African countries have not reported any evidence of the presence of ebolavirus (read more)

venerdì 2 maggio 2014

Novel Reassortant Influenza A(H5N8) Viruses in Domestic Ducks, Eastern China

Domestic ducks are natural reservoirs of avian influenza viruses and serve as reassortant hosts for new virus subtypes. We isolated 2 novel influenza A(H5N8) viruses from domestic ducks in eastern China, sequenced their genomes, and tested their pathogenicity in chickens and mice. Circulation of these viruses may pose health risks for humans (read more)

Novel Human Bufavirus Genotype 3 in Children with Severe Diarrhea, Bhutan

We identified a new genotype of bufavirus, BuV3, in fecal samples (0.8%) collected to determine the etiology of diarrhea in children in Bhutan. Norovirus GII.6 was detected in 1 sample; no other viral diarrheal pathogens were detected, suggesting BuV3 as a cause of diarrhea. This study investigates genetic diversity of circulating BuVs (read more)

Variola virus archives: a new century, a new approach

Eradication of smallpox was the signature public health achievement of the 20th century—the result of relentless collective action by the global community. Although the disease is long gone, variola virus, which causes smallpox, still exists in two WHO-approved laboratories. 35 years after eradication of smallpox and following immense progress on development of medical countermeasures, destruction of variola virus once more returns to the World Health Assembly (WHA) agenda in May, 2014 (read more)

lunedì 28 aprile 2014

Tamiflu report comes under fire

A study that calls into question the stockpiling of billions of dollars’ worth of antiviral drugs to mitigate the threat of influenza pandemics has been criticized by flu researchers. The analysis of Tamiflu and Relenza, drugs known as neuraminidase inhibitors, was published on 10 April by the Cochrane Collaboration, a group that reviews the effectiveness of health-care measures. It concluded that the medicines were of little use. At the same time, the journal BMJ published a series of articles, including two that summarize the Cochrane findings, and several editorials that focus on the five-year campaign by Cochrane and the BMJ to obtain the unpublished drug-company clinical-trial data later used in the review (read more)

Rubella outbreak in Japan

About 15 000 cases of rubella and 43 cases of congenital rubella syndrome were reported to the National Epidemiological Surveillance of Infectious Diseases between Oct 15, 2012, and March 2, 2014, as a result of the 2012—13 rubella outbreak in Japan.1 This resurgence of rubella has mainly affected adult men aged 35—51 years—who had not received routine rubella vaccine during their childhood when only school girls were vaccinated, and men and women aged 24—34 years—whose vaccine coverage rates were relatively low (read more)

sabato 19 aprile 2014

Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430

Filoviruses are emerging pathogens and causative agents of viral haemorrhagic fever. Case fatality rates of filovirus disease outbreaks are among the highest reported for any human pathogen, exceeding 90% (ref. 1). Licensed therapeutic or vaccine products are not available to treat filovirus diseases. Candidate therapeutics previously shown to be efficacious in non-human primate disease models are based on virus-specific designs and have limited broad-spectrum antiviral potential. Here we show that BCX4430, a novel synthetic adenosine analogue, inhibits infection of distinct filoviruses in human cells. Biochemical, reporter-based and primer-extension assays indicate that BCX4430 inhibits viral RNA polymerase function, acting as a non-obligate RNA chain terminator. Post-exposure intramuscular administration of BCX4430 protects against Ebola virus and Marburg virus disease in rodent models. Most importantly, BCX4430 completely protects cynomolgus macaques from Marburg virus infection when administered as late as 48 hours after infection. In addition, BCX4430 exhibits broad-spectrum antiviral activity against numerous viruses, including bunyaviruses, arenaviruses, paramyxoviruses, coronaviruses and flaviviruses. This is the first report, to our knowledge, of non-human primate protection from filovirus disease by a synthetic drug-like small molecule. We provide additional pharmacological characterizations supporting the potential development of BCX4430 as a countermeasure against human filovirus diseases and other viral diseases representing major public health threats (read more)

giovedì 17 aprile 2014

A highly specific blood test for vCJD

[...] To explore the assay’s specificity and hence suitability for screening exposed and at-risk populations, we tested 5000 blood samples from the American Red Cross in which, because of minimal BSE exposure, no true positives would be expected (US normals). No samples tested positive (100% specificity; 95% CI: 99.93%-100%). The high specificity was reflected in a smaller, healthy UK cohort (UK normals). The assay’s positive likelihood ratio indicates true positives are more than 7000 times as likely as false positives; the negative likelihood ratio indicates true negatives are more than 3 times as likely as false negatives. Finally, we tested a small blind panel of unaffected and vCJD patient samples. Seven of 10 vCJD patient samples tested positive (70% sensitivity), reconfirming but not refining our previous sensitivity estimate [...] (read more)

Novel Paramyxovirus Associated with Severe Acute Febrile Disease, South Sudan and Uganda, 2012

In 2012, a female wildlife biologist experienced fever, malaise, headache, generalized myalgia and arthralgia, neck stiffness, and a sore throat shortly after returning to the United States from a 6-week field expedition to South Sudan and Uganda. She was hospitalized, after which a maculopapular rash developed and became confluent. When the patient was discharged from the hospital on day 14, arthralgia and myalgia had improved, oropharynx ulcerations had healed, the rash had resolved without desquamation, and blood counts and hepatic enzyme levels were returning to reference levels. After several known suspect pathogens were ruled out as the cause of her illness, deep sequencing and metagenomics analysis revealed a novel paramyxovirus related to rubula-like viruses isolated from fruit bats (read more).

An Inactivated Enterovirus 71 Vaccine in Healthy Children

BACKGROUND : Enterovirus 71 (EV71) is a major cause of hand, foot, and mouth disease in children and may be fatal. A vaccine against EV71 is needed.
METHODS : We conducted a randomized, double-blind, placebo-controlled phase 3 trial involving healthy children 6 to 71 months of age in Guangxi Zhuang Autonomous Region, China. Two doses of an inactivated EV71 vaccine or placebo were administered intramuscularly, with a 4-week interval between doses, and children were monitored for up to 11 months. The primary end point was protection against hand, foot, and mouth disease caused by EV71.
RESULTS : A total of 12,000 children were randomly assigned to receive vaccine or placebo. Serum neutralizing antibodies were assessed in 549 children who received the vaccine. The seroconversion rate was 100% 4 weeks after the two vaccinations, with a geometric mean titer of 170.6. Over the course of two epidemic seasons, the vaccine efficacy was 97.4% (95% confidence interval [CI], 92.9 to 99.0) according to the intention-to-treat analysis and 97.3% (95% CI, 92.6 to 99.0) according to the per-protocol analysis. Adverse events, such as fever (which occurred in 41.6% of the participants who received vaccine vs. 35.2% of those who received placebo), were significantly more common in the week after vaccination among children who received the vaccine than among those who received placebo.
CONCLUSIONS : The inactivated EV71 vaccine elicited EV71-specific immune responses and protection against EV71-associated hand, foot, and mouth disease (read more)

Mystery solved: VSV-G-LVs do not allow efficient gene transfer into unstimulated T cells, B cells, and HSCs because they lack the LDL receptor

 (read more)

Hepatitis C Virus Maintains Infectivity for Weeks After Drying on Inanimate Surfaces at Room Temperature: Implications for Risks of Transmission

Background. Healthcare workers may come into contact with fomites that contain infectious hepatitis C virus (HCV) during preparation of plasma or following placement or removal of venous lines. Similarly, injection drugs users may come into contact with fomites. Hypothesizing that prolonged viability of HCV in fomites may contribute significantly to incidence, we determined the longevity of virus infectivity and the effectiveness of antiseptics.
Methods. We determined the volume of drops misplaced during transfer of serum or plasma. Aliquots equivalent to the maximum drop volume of plasma spiked with the 2a HCV reporter virus were loaded into 24-well plates. Plates were stored uncovered at 3 temperatures: 4°C, 22°C, and 37°C for up to 6 weeks before viral infectivity was determined in a microculture assay.
Results. The mean volume of an accidental drop was 29 µL (min–max of 20–33 µL). At storage temperatures 4°C and 22°C, we recovered viable HCV from the low-titer spots for up to 6 weeks of storage. The rank order of HCV virucidal activity of commonly used antiseptics was bleach (1:10) > cavicide (1:10) > ethanol (70%).
Conclusions. The hypothesis of potential transmission from fomites was supported by the experimental results. The anti-HCV activity of commercial antiseptics varied (read more)

Human Polyomavirus 9 Infection in Kidney Transplant Patients

Several human polyomaviruses of unknown prevalence and pathogenicity have been identified, including human polyomavirus 9 (HPyV9). To determine rates of HPyV9 infection among immunosuppressed patients, we screened serum samples from 101 kidney transplant patients in the Netherlands for HPyV9 DNA and seroreactivity. A total of 21 patients had positive results for HPyV9 DNA; positivity rates peaked at 3 months after transplantation, but the highest viral loads were measured just after transplantation. During 18 months of follow-up, HPyV9 seroprevalence increased from 33% to 46% among transplant patients; seroprevalence remained stable at ≈30% in a control group of healthy blood donors in whom no HPyV9 DNA was detected. Further analysis revealed an association between detection of HPyV9 and detection of BK polyomavirus but not of cytomegalovirus. Our data indicate that HPyV9 infection is frequent in kidney transplant patients, but the nature of infection—endogenous or donor-derived—and pathogenic potential of this virus remain unknown (read more)

Coronavirus entry and release in polarized epithelial cells: a review

Most coronaviruses cause respiratory or intestinal infections in their animal or human host. Hence, their interaction with polarized epithelial cells plays a critical role in the onset and outcome of infection. In this paper, we review the knowledge regarding the entry and release of coronaviruses, with particular emphasis on the severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses. As these viruses approach the epithelial surfaces from the apical side, it is not surprising that coronavirus cell receptors are exposed primarily on the apical domain of polarized epithelial cells. With respect to release, all possibilities appear to occur. Thus, most coronaviruses exit through the apical surface, several through the basolateral one, although the Middle East respiratory syndrome coronavirus appears to use both sides. These observations help us understand the local or systematic spread of the infection within its host as well as the spread of the virus within the host population (read more)

Hyperimmune intravenous immunoglobulin containing high titers of pandemic H1N1 hemagglutinin and neuraminidase antibodies provides dose-dependent protection against lethal virus challenge in SCID mice

Background: Convalescent plasma and fractionated immunoglobulins have been suggested as prophylactic or therapeutic interventions during an influenza pandemic.FindingsIntravenous immunoglobulin (IVIG) preparations manufactured from human plasma collected before the 2009 H1N1 influenza pandemic, and post-pandemic hyperimmune (H)-IVIG preparations were characterized with respect to hemagglutination inhibition (HI), microneutralization (MN) and neuraminidase-inhibiting (NAi) antibody titers against pandemic H1N1 (pH1N1) and seasonal H1N1 (sH1N1) viruses. The protective efficacy of the IVIG and H-IVIG preparations was evaluated in a SCID mouse challenge model.Substantial levels of HI, MN and NAi antibodies against pH1N1 (GMTs 1:45, 1:204 and 1: 727, respectively) and sH1N1 (GMTs 1:688, 1:4,946 and 1:312, respectively) were present in pre-pandemic IVIG preparations. In post-pandemic H-IVIG preparations, HI, MN and NAi antibody GMTs against pH1N1 were 1:1,280, 1:11,404 and 1:2,488 ( 28-, 56- and 3.4-fold enriched), respectively, compared to pre-pandemic IVIG preparations (p < 0.001). Post-pandemic H-IVIG (HI titer 1:1,280) provided complete protection from lethality of SCID mice against pH1N1 challenge (100 % of mice survived for 29 days post-challenge). Pre-pandemic IVIG (HI titer 1:70) did not provide significant protection against pH1N1 challenge (50 % of mice survived 29 days post-challenge compared to 40 % survival in the buffer control group). There was a highly significant correlation between circulating in vivo HI and MN antibody titers and survival (p < 0001). Conclusion: The substantial enrichment of HA- and NA-specific antibodies in H-IVIG and the efficacious protection of SCID mice against challenge with pH1N1 suggests H-IVIG as a promising intervention against pandemic influenza for immunocompromised patients and other risk groups (read more)

Bat Flight and Zoonotic Viruses

Bats are sources of high viral diversity and high-profile zoonotic viruses worldwide. Although apparently not pathogenic in their reservoir hosts, some viruses from bats severely affect other mammals, including humans. Examples include severe acute respiratory syndrome coronaviruses, Ebola and Marburg viruses, and Nipah and Hendra viruses. Factors underlying high viral diversity in bats are the subject of speculation. We hypothesize that flight, a factor common to all bats but to no other mammals, provides an intensive selective force for coexistence with viral parasites through a daily cycle that elevates metabolism and body temperature analogous to the febrile response in other mammals. On an evolutionary scale, this host–virus interaction might have resulted in the large diversity of zoonotic viruses in bats, possibly through bat viruses adapting to be more tolerant of the fever response and less virulent to their natural hosts (read more)

Emergence of Zaire Ebola Virus Disease in Guinea — Preliminary Report

In March 2014, the World Health Organization was notified of an outbreak of a communicable disease characterized by fever, severe diarrhea, vomiting, and a high fatality rate in Guinea. Virologic investigation identified Zaire ebolavirus (EBOV) as the causative agent. Full-length genome sequencing and phylogenetic analysis showed that EBOV from Guinea forms a separate clade in relationship to the known EBOV strains from the Democratic Republic of Congo and Gabon. Epidemiologic investigation linked the laboratory-confirmed cases with the presumed first fatality of the outbreak in December 2013. This study demonstrates the emergence of a new EBOV strain in Guinea (read more)