Lactoferrin for prevention of common viral infections

Although lactoferrin has many biological functions, the host-protective effects against pathogenic microorganisms including bacteria, fungi, and viruses are regarded as one of the most important. Here, we review research on the protective role of lactoferrin administration against common viral infections. Many studies have shown the in vitro antiviral activity of lactoferrin against viral pathogens that cause common infections such as the common cold, influenza, gastroenteritis, summer cold, and herpes, where lactoferrin inhibits mainly viral attachment to the target cells. Recently, studies indicating the in vivo protective effects of lactoferrin by oral administration against common viral infections have been increasing. For instance, norovirus is an extremely important emerging human pathogen that causes a majority of gastroenteritis outbreaks worldwide that may be a target candidate for lactoferrin. Lactoferrin consumption reduced the incidence of noroviral gastroenteritis in children and a similar effect was observed in a wide range of ages in a preliminary survey. A recent in vitro study reported that lactoferrin inhibits both cellular attachment of the murine norovirus, a virus closely-related to the human norovirus, and viral replication in the cells by inducing antiviral cytokines interferon (IFN)-α/β. Lactoferrin administration also enhances NK cell activity and Th1 cytokine responses, which lead to protection against viral infections. In conclusion, lactoferrin consumption may protect the host from viral infections through inhibiting the attachment of a virus to the cells, replication of the virus in the cells, and enhancement of systemic immune functions.     

Human norovirus infection in Latin America

Noroviruses are important enteric pathogens involved in non-bacterial gastroenteritis outbreaks worldwide. Noroviruses mainly occur from person to person via the fecal-oral route but also through contaminated food or water; indirect contamination is also possible due to the resistance of the virus in the environment. Latin American countries as a whole cover a vast North-to-South range, which is highly heterogeneous in terms of climate, ecosystem, human population distribution (urban areas with high human densities versus closed communities), economic development and genetic backgrounds resulting from each particular historical context. This review aims to present epidemiological and clinical patterns of human norovirus infections in Latin American countries. Divergent prevalences were observed depending on the country and the surveyed population. In particular, a shift in rotavirus/norovirus ratio in the etiologies of gastroenteritis was detected in some countries and could be attributed partly to rotavirus vaccine coverage in their infant population. While GII.4 noroviruses were seen to constitute the most common genotype, differences in genotype distribution were observed both in the environment (via sewage sampling proxy) and between genotypes circulating in healthy and diarrheic patients. Due to high climatic discrepancies, different patterns of seasonality were observed. Accordingly, this continent may condense the different particular epidemiological features encountered for HuNoV infections worldwide.     

Noroviren – ein Impfstoff muss erst entwickelt werden

After the first scientific documentation of a ‚winter vomiting disease‘-outbreak in Norwalk, Ohio and the detection of the causal agent many studies have been performed to establish effective preventive measures against Noro-Virus-infection. In 2010 first results of a successful vaccine trial using virus-like-particles were presented, followed by another vaccine-development in 2012. In this communication data on properties of Noroviruses and results of vaccine trials are presented.     

Molecular epidemiology of norovirus associated with gastroenteritis and emergence of norovirus GII.4 variant 2012 in Japanese pediatric patients

In late 2012, an outbreak of acute gastroenteritis due to norovirus variant Sydney_2012 occurred and have been reported from many counties. In this study, we described surveillance study of the incidence of norovirus infections among Japanese pediatric patients in association with gastroenteritis and investigated the antigenic change of the new variant Sydney_2012 circulated in Japanese populations. A total of 2381 fecal specimens collected from children with acute gastroenteritis in Hokkaido, Tokyo, Shizuoka, Kyoto, Osaka, and Saga from 2009 to 2013 were examined for norovirus and further analyzed molecularly. A high proportion (39.3%) of norovirus positive samples and several genotypes were detected. Norovirus GII.4 dominated over other genotypes (71.4%). The Den_Haag_2006b (43.2%) was detected as the predominant variant and co-circulated with New_Orleans_2009 (17.8%) until March 2012. Subsequently, they were displaced by Sydney_2012. The Sydney_2012 variant has been responsible for the majority of norovirus infections in 2012–2013 (85.7%). Although Sydney_2012 variant has a common ancestor with New_Orleans_2009 variant, analysis of P2 sub-domain showed a high level of diversity in comparison with other variants in four amino acid changes at the antigenic sites. The change in particular residue 393 of new variant may affect HBGA recognition. Analysis of noroviruses circulating in the past 4 years revealed a change of predominant variant of norovirus GII.4 in each epidemic season. The change of amino acid in putative epitopes may have led the virus escape from the existing herd immunity and explain the increase of new variant outbreaks.     

Genetic diversity of norovirus in hospitalised diarrhoeic children and asymptomatic controls in Dar es Salaam,Tanzania

This study investigated and reports norovirus diarrhoea, genetic diversity and associated clinical symptoms, HIV status and seasonality in a paediatric population of Tanzania.Stool specimens and demographic/clinical information, were prospectively collected from 705 hospitalised children with diarrhoea (cases) and 561 children without diarrhoea (controls) between 2010 and 2011. Norovirus detection was done by real-time RT-PCR. Genotype was determined using Gel-based and real time RT-PCR methods and sequencing targeting the polymerase and the capsid region respectively. Norovirus was detected in 14.3%, 181/1266 children. The prevalence of norovirus was significantly higher in cases (18.3%, 129/705) than in controls, (9.2%, 52/561), P < 0.05. Except for one child who had double infection with GI and GII all 129 cases had GII. Among controls, 23.1% had GI and 76.9% had GII. Norovirus GII.4 was significantly more prevalent in cases 87.9% than in controls 56.5%. Other genotypes detected in both cases and controls were GII.21, GII.16 and GII.g. The highest numbers of norovirus were detected in April 2011. The number of norovirus detected was significantly higher during the first than second year of life (109/540, 20.2% vs. 20/165, 12.1%). The prevalence of norovirus in HIV-positive and negative children was (21.2%, 7/33) and (10.3%, 40/390, P = 0.05) respectively, regardless of diarrhoea symptoms. No significant difference in gender, parent’s level of education or nutritional status with norovirus infection was observed within cases or controls. This study confirms the significant role of norovirus infection, especially GII.4 in diarrhoeic children who need hospitalisation and adds knowledge on norovirus epidemiology in the African region.     

Evaluation of the RIDAGENE real-time PCR assay for the detection of GI and GII norovirus

The current study examined the efficacy of the RIDAGENE norovirus (NoV) real-time polymerase chain reaction assay (R-Biopharm, Darmstadt, Germany) for use in a routine diagnostic laboratory. The RIDAGENE assay had an overall sensitivity of 98% but was more sensitive for GII than GI NoV. The assay had a specificity of 98%. The RIDAGENE assay could detect a variety of GI and GII open reading frame 2 genotypes including GI.1, GI.3, GI.8, GI.13, GII.2, GII.3, GII.4 (including the following variants: 2006b, 2009, 2012, and 3 others that have not been assigned), GII.6, GII.12, and GII.13. The assay did not cross react with a number of gastroenteritis viruses including adenovirus, astrovirus, rotavirus, and sapovirus. The assay was straightforward to perform, and for a run of 50 specimens, a result was obtainable in roughly 4 hours. The RIDAGENE assay can be recommended as a valuable detection method for NoV.     

北京市2013－2014年肠道门诊腹泻患者中诺如病毒感染的流行病学及临床特征分析

目的 了解北京市肠道门诊腹泻患者诺如病毒感染的流行状况及临床特点。方法 采集2013年4月至2014年3月北京市肠道门诊1 892名腹泻患者粪便标本, 并收集患者的流行病学及临床症状资料。使用real time RT-PCR对诺如病毒核酸进行检测, 采用描述性流行病学方法进行分析。结果 2013年4月至2014年3月北京市肠道门诊腹泻患者诺如病毒阳性率为14.2%(269/1 892);寒冷月份阳性率较高;怀柔区、延庆县等西北部山区阳性率较高;6月龄至5岁儿童诺如病毒阳性率高于其他年龄组, 差异有统计学意义(P=0.006), 散居托幼儿童诺如病毒阳性率高于其他职业人群, 差异有统计学意义(P=0.025);诺如病毒阳性腹泻患者恶心、呕吐症状发生率高于阴性患者, 差异有统计学意义(P<0.05)。结论 诺如病毒是肠道门诊腹泻患者的重要病原, 6月龄至5岁腹泻儿童诺如病毒感染率高于其他人群, 恶心、呕吐为诺如病毒感染的常见症状。     

Genome characterization of a GII.6 norovirus strain identified in China

Noroviruses (NoVs) are the primary cause of non-bacterial acute gastroenteritis worldwide. Most NoV infections are caused by GII.4, but GII.6 is also an important genotype with a long-term persistence in human populations. In this study, the complete genome sequence of a NoV strain GZ2010-L96 isolated in China was identified and analyzed phylogenetically. The viral genome comprised 7550 nucleotides, and its phylogenetic analysis revealed that the strain belonged to GII.6 genotype. All reported GII.6 NoV capsid protein sequences were also collected for comparative analysis, and GZ2010-L96 was clustered into GII.6-b with other 8 strains. Meanwhile, it was found that 53 spots on viral capsid showed subcluster specificity according to multiple alignments. Moreover, homologous modeling of GZ2010-L96 based on comparison with GII.4 VA387 strain showed a different antigen distribution pattern. In summary, the genome of the GII.6 strain GZ2010-L96 detected in China was extensively characterized, and phylogenetic analyses of GII.6 NoVs based on the capsid proteins may reveal a different evolution process from the predominant genotype GII.4.     

2013－2019年浙江省湖州市急性胃肠炎病例GⅡ.P7-GⅡ.6型诺如病毒基因特征分析

  目的  分析2013 — 2019年浙江省湖州市急性胃肠炎病例诺如病毒基因特征,为疾病监测和防控提供参考。  方法  采用荧光定量反转录聚合酶链式反应（RT-PCR）方法对2013年12月、2014年4、12月、2019年3月发生的4起学校/托幼机构急性胃肠炎患者送检粪便标本进行诺如病毒核酸检测。 采用RT-PCR法对核酸阳性标本的多聚酶和衣壳蛋白部分区域进行扩增,并对扩增产物进行序列测定。 利用在线分型工具和系统进化分析对病原序列进行基因特征分析。  结果  共计28份标本中分别有5、4、2、5份为GⅡ型诺如病毒核酸阳性,阳性率为57.1%（16/28）。 4次疫情各有1份标本测序成功;在线分型和系统进化分支分析显示,4起疫情的病原均为GⅡ.P7-GⅡ.6重组型诺如病毒,但进化分支不同,其中2013年疫情标本检出GⅡ.P7-GⅡ.6c型;2014年2起疫情均为GⅡ.P7-GⅡ.6b型,2019年疫情中检出的GⅡ.P7-GⅡ.6a型。  结论  GⅡ.P7-GⅡ.6型重组型诺如病毒是引起湖州市2013 — 2019年4起急性胃肠炎暴发疫情的病原体,每年毒株存在一定基因进化分支的差异。 鉴于该病毒在全球范围内具有持续和广泛的流行能力,应进一步加强对该型别重组型诺如病毒的监测。