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)

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)

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)

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)

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)

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)