Risk factors for sporadic norovirus infection: a systematic review and meta-analysis

Norovirus is responsible for 20% of acute gastroenteritis worldwide. The fecal-oral route of transmission is known, but we proposed a first attempt to identify the relative importance of different sources and vehicles for sporadic cases using meta-analysis models. Case-control and cohort/cross-sectional studies were systematically reviewed and analyzed to assess the main risk factors associated with sporadic norovirus infections. Suitable scientific articles were identified through systematic literature search and subjected to a methodological quality assessment. Mixed-effects meta-analyses models were adjusted by population type to appropriate risk factor categories. The quality assessment stage led to include 14 primary studies conducted between 1993 and 2014. From these, eight studies investigated exposures in children/infants, and eight concerned the mixed population. The meta-analysis confirmed the oro-fecal route for norovirus infections, with the person-to-person transmission (pooled OR=3.002; 95% CI: [2.502 -3.060] in mixed population), and the lack of personal hygiene (pooled OR=2.329; 95% CI: [1.048 -5.169]). The meta-analysis also enlightened the role of indirect transmission through the environment with pathways like untreated drinking water (mixed population), with a pooled OR=2.680 (95% CI: [1.081-6.643]) and farm environment (children population). Indirect transmission also involved the food pathway, which was finally found significant with consumption of seafood (mixed population) (pooled OR=2.270; 95% CI: [1.299-3.968]) and composite food (eating outside/uncooked mixed and young population) (pooled OR=4.541; 95% CI: [3.461-5.958]). These results are coherent with the findings from studies on outbreaks. However, a too broad definition of exposure factors limited the interpretation of results, as occurred with the seafood pathways that combined fish and shellfish. Other factors such as consumption of Food-handled products or the type of drinking water deserveE to be better investigated. Furthermore, better harmonization in case definition and appropriate case-control or cross-sectional studies would allow better addressing sporadic cases risk factors, especially for susceptible populations, such as children, elderly or immunosuppressed persons.U. Gonzales-Barron and V. Cadavez are grateful to the Foundation for Food Science and Technology (FCT, Portugal) and FEDER under Programme PT2020 for financial support to CIMO (UID/AGR/00690/ 2019). U. Gonzales-Barron thanks the national funding by FCT, P.I., through the Institutional Scientific Employment Program contract.info:eu-repo/semantics/publishedVersio

Expression of Mutated Poliovirus Receptors in Human Neuroblastoma Cells Persistently Infected with Poliovirus

AbstractPoliovirus (PV) is able to establish persistent infections in human neuroblastoma IMR-32 cells [Colbère-Garapin et al. (1989) Proc. Natl. Acad. Sci. USA 86, 7590]. During persistent infection, PV mutants are selected that display substitutions of residues in regions of the capsid known to interact with the PV receptor (PVR), a glycoprotein of the immunoglobulin superfamily. The mechanism of persistent infection in IMR-32 cells may therefore involve the selection of mutant PVRs. To test this hypothesis, the sequences of the PVR mRNAs in uninfected IMR-32 cells and in two independent IMR-32 cell cultures persistently infected with the Mahoney strain of PV type 1 (PV1/Mahoney) were determined. The PVR mRNA population of uninfected cells was homogeneous, and no mutation was repeatedly found, whereas that of persistently infected cells displayed missense mutations. Particular mutations were repeatedly detected, and all of them mapped to the N-terminal domain of PVR (domain 1), which interacts directly with PV. These mutations generated several types of PVR variants with the following substitutions: Ala67→Thr alone, Ala67→Thr associated with Gly39→Ser, and Arg104→Gln. Functional analysis of PVR in murine LM cells, stably expressing each of the PVR forms, showed that the PVR forms selected during persistent infection conferred on LM cells partial resistance to PV1/Mahoney-induced lysis. Although adsorption onto PVR seemed to be independent of the PVR form, an analysis of the conformational changes of the capsid during the early steps of the PV cycle provided evidence that the Ser39/Thr67 and Gln104 substitutions almost halved the conversion of 160S infectious particles into 135S A particles associated with the PV–PVR interaction. Altogether, these findings indicate that during persistent infection, specific mutations were selected in the domain 1 of PVR and that these mutations increased the resistance of cells to PV-induced lysis. These results are discussed in view of the position of the mutations on PVR

Risk factors for sporadic hepatitis A infection: a systematic review and meta-analysis

Hepatitis A virus (HAV) is responsible for common acute viral hepatitis worldwide. Improvement in sanitation and use of efficient vaccines have reduced HAV incidence in developed countries. However, naive adult population are most susceptible to severe outcomes, and high endemic areas persist in developing regions. The transmission of HAV through the fecal-oral route is established. However, considering evolving consumption habits and global market exchange of food, investigations on risk factors associated with HAV infection are needed. Thus, a systematic review and a meta-analysis of case-control, cohort and transversal studies was performed to determine the main risk factors associated with sporadic HAV infection. Relevant scientific articles were identified through systematic literature search and subjected to a methodological quality assessment. Mixed-effects meta-analyses models were adjusted by population type to appropriate data partitions. HAV infections are defined by serological testing. The quality assessment stage selected 78 studies investigating risk factors for sporadic infections with hepatitis A conducted between 1985 and 2013. This meta-analysis confirmed that HAV infections are mostly related to inter-human transmissions, either due to contact with an ill person, through oral-anal sex practice, or lack of personal hygiene. Travel to endemic countries, occupational exposure such as working in child daycare, and exposure to wastewater were associated with HAV infection. As HAV can persist in the environment, it was not surprising that consumption of untreated drinking water, shellfish consumed raw, and crop products were risk factors. Food contamination could be due to the use of contaminated water (fruits, vegetables) or originate from infected food handlers at every point of the food chain (from picking to serving). Eating or drinking outside were associated with HAV infection. A lack of recent case-control studies was identified, with only three studies eligible between 2011 and 2017. Case-control studies required a more precise definition of risk factors such as type of crop product, and storing/preparation information (e.g. washed, frozen). The frequency of consumption or duration of environmental exposure could also better inform relationship between exposure and risk of infection. In a context of epidemiological change of HAV, international travel and trade of foods, future case-control studies are needed and should focus on populations at risk of severe infections and acute cases.U. Gonzales-Barron and V. Cadavez are grateful to the Foundation for Science and Technology (FCT, Portugal) and FEDER under programme PT2020 for the financial support to CIMO (UID/AGR/00690/2019).info:eu-repo/semantics/publishedVersio

Hepatitis E : an emerging zoonosis ?

Hepatitis E virus (HEV) causes acute, enterically transmitted hepatitis. It is associated with epidemics in endemic regions and sporadic cases in non-endemic regions. Although the waterborne origin of epidemics is well documented, the origin of sporadic cases is frequently autochthonous and remains unknown. Unlike the other hepatitis viruses, HEV has an animal reservoir. Phylogenetic studies on human and animal strains, and the identification of cases transmitted directly from animal to man strongly suggest that HEV is a zoonotic agent. It is essential to set up a surveillance system of the animal reservoir and of human cases to determine the origin of all autochthonous cases. In addition, potential routes of contaminations must be identified to define preventive measures.Le virus de l'hépatite E (VHE) est responsable d'une hépatite aiguë à transmission entérique. La maladie existe sous formes d'épidémies dans les régions endémiques (Asie, Afrique), et de cas sporadiques dans les régions non endémiques. Alors que l'origine hydrique des épidémies est bien caractérisée, celle des cas sporadiques est fréquemment autochtone et reste inconnue. Le VHE se différencie des autres virus des hépatites par la présence d'un réservoir animal. Des études phylogénétiques sur les souches humaines et animales, ainsi que l'identification de cas de transmission directe de l'animal à l'homme suggèrent fortement que le VHE est un agent zoonotique. Il faudrait mettre en place un système de surveillance du réservoir animal, couplé à un observatoire des cas humains, afin de déterminer l'origine de tous les cas autochtones. Les voies possibles de contamination doivent également être identifiées, afin de définir des mesures de prévention

Possible Zoonotic Transmission of Hepatitis E from Pet Pig to Its Owner

Hepatitis E is transmitted mainly by water or food, but in industrialized countries, all routes of transmission have not been identified. We describe possible zoonotic transmission of hepatitis E virus that involved direct contact between a pet pig and its owner

Zoonotic hepatitis E: animal reservoirs and emerging risks

Hepatitis E virus (HEV) is responsible for enterically-transmitted acute hepatitis in humans with two distinct epidemiological patterns. In endemic regions, large waterborne epidemics with thousands of people affected have been observed, and, in contrast, in non-endemic regions, sporadic cases have been described. Although contaminated water has been well documented as the source of infection in endemic regions, the modes of transmission in non-endemic regions are much less known. HEV is a single-strand, positive-sense RNA virus which is classified in the Hepeviridae family with at least four known main genotypes (1–4) of mammalian HEV and one avian HEV. HEV is unique among the known hepatitis viruses, in which it has an animal reservoir. In contrast to humans, swine and other mammalian animal species infected by HEV generally remain asymptomatic, whereas chickens infected by avian HEV may develop a disease known as Hepatitis-Splenomegaly syndrome. HEV genotypes 1 and 2 are found exclusively in humans while genotypes 3 and 4 are found both in humans and other mammals. Several lines of evidence indicate that, in some cases involving HEV genotypes 3 and 4, animal to human transmissions occur. Furthermore, individuals with direct contact with animals are at higher risk of HEV infection. Cross-species infections with HEV genotypes 3 and 4 have been demonstrated experimentally. However, not all sources of human infections have been identified thus far and in many cases, the origin of HEV infection in humans remains unknown