Pediatric norovirus GII.4 infections in Nicaragua, 1999–2015

ObjectivesInvestigate clinical and epidemiological factors of pediatric GII.4 norovirus infections in children with acute gastroenteritis (AGE) in Nicaragua between 1999 and 2015.MethodsWe retrospectively analyzed laboratory and epidemiologic data from 1,790 children ≤ 7 years with AGE from 6 hospitals in Nicaragua (n = 538), and 3 community clinics (n = 919) and households (n = 333) in León, between 1999 and 2015. Moreover, asymptomatic children from community clinics (n = 162) and households (n = 105) were enrolled. Norovirus was detected by real-time PCR and genotyped by sequencing the N-terminal and shell region of the capsid gene.ResultsNorovirus was found in 19% (n = 338) and 12% (n = 32) of children with and without AGE, respectively. In total, 20 genotypes including a tentatively new genotype were detected. Among children with AGE, the most common genotypes were GII.4 (53%), GII.14 (7%), GII.3 (6%) and GI.3 (6%). In contrast, only one (1.4%) GII.4 was found in asymptomatic children. The prevalence of GII.4 infections was significantly higher in children between 7 and 12 months of age. The prevalence of GII.4 was lowest in households (38%), followed by community clinics (50%) and hospitals (75%). Several different GII.4 variants were detected and their emergence followed the global temporal trend.ConclusionsOverall our study found the predominance of pediatric GII.4 norovirus infections in Nicaragua mostly occurring in children between 7 and 12 months of age, implicating GII.4 as the main norovirus vaccine target.     

Immunogenicity of a bivalent virus-like particle norovirus vaccine in children from 1 to 8 years of age: A phase 2 randomized,double-blind study

BackgroundYoung children can suffer severe consequences of norovirus gastroenteritis. We performed a dose-finding study of a bivalent virus-like particle (VLP) vaccine candidate (TAK-214) in healthy 1–8-year-old children.MethodsIn this phase 2 study two age cohorts (1–3 and 4–8 years of age inclusive, N = 120 per cohort) of children enrolled from Finland, Panama and Colombia were initially randomized 1:1:1:1 to four groups which were further split into two equal subgroups, to receive one or two intramuscular doses of four TAK-214 formulations containing 15/15, 15/50, 50/50 or 50/150 μg of GI.1/GII.4c genotype VLPs and 0.5 mg Al(OH)₃ at 28 days interval. ELISA Pan-Ig and histoblood group antigen-blocking (HBGA) antibodies against each VLP were measured on days 1, 29, 57 and 210. Parents/guardians recorded solicited local and systemic adverse events (AE) and any unsolicited or serious AEs (SAE).ResultsAll formulations were well-tolerated across both age cohorts and dosage groups with no vaccine-related SAEs reported. Solicited AEs were mostly mild-to-moderate, resolved quickly, and did not increase after the second dose. Pan-Ig and HBGA responses induced after one dose were only slightly increased by the second dose. Across dose groups at Day 29 after one dose GI.1 Pan Ig seroresponse rates (SRR) were 82–97% and 81–96% and GII.4c SRR were 79–97% and 80–91% in 1–3 and 4–8 year-olds, respectively. Respective rates were to 92–93% and 73–92% for GI.1, and 77–100% and 62–83% for GII.4c at Day 57 following two doses. HBGA responses had similar profiles. Both Pan Ig and HBGA geometric mean titers persisted above baseline up to Day 210.ConclusionsAll dosages of TAK-214 displayed acceptable reactogenicity in 1–8-year-old children and induced robust, durable immune responses after one dose which are further increased after two doses.     

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.     

Preclinical dose-ranging studies of a novel dry powder norovirus vaccine formulation

Norovirus is the primary cause of viral gastroenteritis in humans with multiple genotypes currently circulating worldwide. The development of a successful norovirus vaccine is contingent on its ability to induce both systemic and mucosal antibody responses against a wide range of norovirus genotypes. Norovirus virus-like particles (VLPs) are known to elicit systemic and mucosal immune responses when delivered intranasally. Incorporation of these VLPs into an intranasal powder vaccine offers the advantage of simplicity and induction of neutralizing systemic and mucosal antibodies. Nasal immunization, which provides the advantage of ease of administration and a mucosal delivery mechanism, faces the real issue of limited nasal residence time due to mucociliary clearance. Herein, we describe a novel dry powder (GelVac™) formulation of GI or GII.4 norovirus VLPs, two dominant circulating genotypes, to identify the optimal antigen dosages based on systemic and mucosal immune responses in guinea pigs. Systemic and mucosal immunogenicity of each of the VLPs was observed in a dose-dependent manner. In addition, a boosting effect was observed after the second dosing of each VLP antigen. With the GelVac™ formulation, a total antigen dose of ≥ 15 μg was determined to be the maximally immunogenic dose for both GI and GII.4 norovirus VLPs based on evaluation for 56 days. Taken together, these results indicate that norovirus VLPs could be used as potential vaccine candidates without using an immunostimulatory adjuvant and provide a basis for the development of a GelVac™ bivalent GI/GII.4 norovirus VLP vaccine.     

Viral gastroenteritis in rotavirus negative hospitalized children <5 years of age from the independent states of the former Soviet Union

PurposeRotavirus causes nearly 40% of all hospitalizations for AGE among children <5 years of age in the NIS of the former Soviet Union. The etiologic role of other established gastroenteritis viruses in this age group is unknown.MethodsLaboratory-confirmed rotavirus negative fecal specimens (N = 495) collected between January and December 2009 from children in 6 NIS (Armenia, Azerbaijan, Belarus, Georgia, Republic of Moldova and Ukraine) were tested for norovirus, sapovirus, enteric adenovirus and astrovirus by real-time RT-PCR. Genotyping was carried out by sequencing and phylogenetic analysis.ResultsNorovirus, enteric adenovirus, sapovirus and astrovirus were detected in 21.8%, 4.0%, 3.2%, and 1.4% of the rotavirus negative specimens, respectively. Mixed infections were identified in 4.1% of the specimens. Phylogenetic analysis showed co-circulation of several different genotypes with GII.4 Den Haag (2006b) norovirus, GI.2 sapovirus, adenovirus type 41, and astrovirus type 1 causing majority of the infections.ConclusionNorovirus, enteric adenovirus, sapovirus and astrovirus account for a significant proportion (30.5%) of AGE in hospitalized children <5 years of age in 6 NIS.     

Global Trends in Norovirus Genotype Distribution among Children with Acute Gastroenteritis

Noroviruses are a leading cause of acute gastroenteritis (AGE) among adults and children worldwide. NoroSurv is a global network for norovirus strain surveillance among children <5 years of age with AGE. Participants in 16 countries across 6 continents used standardized protocols for dual typing (genotype and polymerase type) and uploaded 1,325 dual-typed sequences to the NoroSurv web portal during 2016–2020. More than 50% of submitted sequences were GII.4 Sydney[P16] or GII.4 Sydney[P31] strains. Other common strains included GII.2[P16], GII.3[P12], GII.6[P7], and GI.3[P3] viruses. In total, 22 genotypes and 36 dual types, including GII.3 and GII.20 viruses with rarely reported polymerase types, were detected, reflecting high strain diversity. Surveillance data captured in NoroSurv enables the monitoring of trends in norovirus strains associated childhood AGE throughout the world on a near real-time basis.     

Robust mucosal-homing antibody-secreting B cell responses induced by intramuscular administration of adjuvanted bivalent human norovirus-like particle vaccine

BackgroundTwo major antigenically heterogenous norovirus genogroups (GI and GII) commonly infect humans and are the leading cause of foodborne, viral gastrointestinal infections in adults.MethodsWe assessed B cell responses in participants in a double-blind, placebo-controlled, dose-escalation phase 1 study of the safety and immunogenicity of an intramuscular bivalent norovirus virus-like particle (VLP) vaccine. The vaccine contained a GI.1 VLP (Norwalk) and a consensus GII.4 VLP, representing the two major genotypes that cause human disease, and was administered on days 0 and 28 to healthy adults aged 18–49 years. Four separate cohorts received increasing doses of 5 μg, 15 μg, 50 μg, and 150 μg of each VLP adjuvanted in monophosphoryl lipid A and alum. PBMCs were analyzed for B cell activation and mucosal homing markers (flow cytometry) and VLP-specific and total IgG and IgA Ab-secreting cells (ASCs); and serum titers of VLP-specific IgG, IgA, and Pan-Ig were determined.ResultsThe vaccine elicited CD27+ CD38+ plasmablasts and high frequencies of ASCs specific for both VLP antigens in the peripheral blood at 7 days after the first dose. The plasmablasts exhibited a mucosal-homing phenotype and included a high proportion of IgA ASCs. Serum antibodies increased as early as 7 days after the first immunization.ConclusionsThe data suggest that a single dose of the IM bivalent norovirus vaccine is effective in activating pre-existing B cell memory. The rapid B cell response and the mucosal homing phenotype of induced ASCs are consistent with anamnestic responses in subjects primed by prior oral norovirus infection.This study is registered at ClinicalTrials.gov Identifier NCT01609257.     

A detailed analysis of possible efficacy signals of NTHi-Mcat vaccine against severe COPD exacerbations in a previously reported randomised phase 2b trial

BackgroundAn investigational vaccine containing non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) surface proteins did not show vaccine efficacy (VE) against combined moderate and severe (moderate/severe) exacerbations in a randomised, observer-blinded, placebo-controlled phase 2b trial of patients with chronic obstructive pulmonary disease (COPD). Nevertheless, observations on rates of severe exacerbations and hospitalisations encouraged further evaluation.MethodsPatients with stable COPD (moderate to very severe airflow limitation, Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 2–4), 40–80 years and at least one moderate/severe exacerbation in the last year received two doses of NTHi-Mcat vaccine or placebo plus standard care. Secondary analyses were conducted on VE against exacerbations according to severity. Potential predictive factors at baseline for VE against severe exacerbations were explored in post-hoc analyses.ResultsOf 606 patients enrolled, 571 were included in the efficacy analysis (279 in NTHi-Mcat vaccine group, 292 in placebo group). VE against severe acute exacerbations of COPD (AECOPD) in various subgroups was 52.11 % (p = 0.015; frequent exacerbators), 65.43 % (p = 0.015; baseline GOLD grade 4), 38.24 % (p = 0.034; previous pneumococcal and/or influenza vaccination). VE was 52.49 % (p = 0.044) for the 6–12 months period after 1 month post-dose 2. Multivariable analysis identified two factors (frequent exacerbator status plus inhaled corticosteroid use at baseline) associated with significant VE against severe AECOPD; in this subpopulation, VE was 74.99 % (p < 0.001).ConclusionResults suggest potential efficacy with the NTHi-Mcat vaccine against severe exacerbations in certain patients with COPD, in particular those who have frequent exacerbations and use inhaled corticosteroids. This potential signal requires confirmation in an appropriately designed prospective clinical trial.Trial registrationClinicalTrials.gov, NCT03281876.     

A phase 1/2 randomised placebo-controlled study of the COVID-19 vaccine mRNA-1273 in healthy Japanese adults: An interim report

IntroductionThe mRNA vaccine, mRNA-1273/TAK-919, encodes the prefusion-stabilised spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report interim results of the first study evaluating safety and immunogenicity of mRNA-1273 in healthy Japanese participants.MethodsThis phase 1/2, randomised, observer-blind, placebo-controlled trial, conducted in Japan (two sites), enrolled healthy adults aged ≥ 20 years with no prior exposure to investigational coronavirus vaccines/treatments, and no known history/risk of SARS-CoV-2 infection. Participants were stratified by age (< 65/≥ 65 years) and randomised to receive two doses of 100 μg mRNA-1273 or placebo administered as intramuscular injections 28 days apart. Primary outcomes were safety and immunogenicity assessed by anti-SARS-CoV-2-spike protein-binding antibody level (bAb). A secondary outcome was SARS-CoV-2 neutralising antibody (nAb) response.ResultsParticipants were enrolled between 21 January and 3 February 2021, and 200 were randomised: mRNA-1273, n = 150 (< 65 years, n = 100; ≥ 65 years, n = 50); placebo, n = 50 (< 65 years, n = 40; ≥ 65 years, n = 10). Solicited adverse events (AEs) through 7 days after each vaccination occurred in 144/150 (96%) and 19/50 (38%) participants in the mRNA-1273 and placebo arms, respectively. In the mRNA-1273 arm, injection-site pain, myalgia and fatigue were the most frequently reported solicited AEs after each vaccination, irrespective of age. Robust immune responses occurred with mRNA-1273 (n = 147) with a bAb geometric mean fold rise (95% confidence interval [CI]) from baseline of 1009 (865, 1177) and a nAb of 21.7 (19.8, 23.8) at day 57. Seroconversion rates (95% CI) for bAb and nAb were both 100% (97.5, 100) at day 57. No such response occurred with placebo (n = 49).ConclusionTwo doses of 100 μg mRNA-1273 given 28 days apart demonstrated an acceptable safety profile and induced significant anti-SARS-CoV-2 immune responses in a Japanese population aged ≥ 20 years. Funding: Takeda Pharmaceutical Company Limited and Japan Agency for Medical Research and Development (AMED). ClinicalTrials.gov: NCT04677660.     

Acute gastroenteritis hospitalizations after implementation of universal mass vaccination against rotavirus

BackgroundEstonia implemented rotavirus universal mass vaccination (RV UMV) in July 2014. We aimed to describe changes in acute gastroenteritis (AGE) hospitalization during RV seasons before (2007–2013) and after (2015–2018) RV UMV and compare patient profile of hospitalized AGE patients aged 0–18 years during first two consecutive RV seasons 2015 vs 2016.MethodsWe described AGE hospitalization patterns pre-and post-vaccine era using Estonian Health Insurance Fund (HIF) database. During a two-year observational multicenter study in seven Estonian hospitals from 01st of February 2015 to 30th August 2016 we assessed patient profile of all patients who met pre-determined AGE criteria.ResultsIn post-vaccine era AGE hospitalization rate decreased from 10 to 8 per 1000 population (RR 0.81, 95% CI 0.79–0.83) compared to pre-vaccine era. Decreased RV seasonal activity, 81% (95% CI 77–84) and 55% (95% CI 52–58) reduction of rotavirus gastroenteritis (RVGE) hospitalization among age groups <1 and 1–4, respectively and upsurge of norovirus gastroenteritis (NoVGE) hospitalizations (RR = 1.8; 95% CI 1.6–1.9) was seen.In the multicenter observational study, among 2249 AGE patients hospitalized median age of RVGE patients increased from 2 to 3 years (p < 0.01) and duration of hospital stay decreased among RVGE, NoVGE and other GE patients during two consecutive RV seasons. According to Vesikari Clinical Severity Scoring System statistically significant change of severity score distribution in two RV seasons was seen (p < 0.001) with trend towards less severe AGE hospitalizations; 82.5% vs 70.5% severe cases in 2015 vs 2016, respectively.ConclusionRV UMV lead to immediate and sustainable reduction of hospitalizations due to RVGE in children aged <4 years and reduction of overall AGE accompanied with the decrease in the severity of hospitalized children.     

A randomized phase 3 trial of the immunogenicity and safety of coadministration of a live-attenuated tetravalent dengue vaccine (TAK-003) and an inactivated hepatitis a (HAV) virus vaccine in a dengue non-endemic country

BackgroundVaccination against hepatitis A virus (HAV) is largely recommended for travelers worldwide. Concurrent dengue and HAV vaccination may be desired in parallel for travelers to countries where both diseases are endemic. This randomized, observer-blind, phase 3 trial evaluated coadministration of HAV vaccine with tetravalent dengue vaccine (TAK-003) in healthy adults aged 18–60 years living in the UK.MethodsParticipants were randomized (1:1:1) to receive HAV vaccine and placebo on Day 1, and placebo on Day 90 (Group 1), TAK-003 and placebo on Day 1, and TAK-003 on Day 90 (Group 2), or TAK-003 and HAV vaccine on Day 1, and TAK-003 on Day 90 (Group 3). The primary objective was non-inferiority of HAV seroprotection rate (anti-HAV ≥ 12.5 mIU/mL) in Group 3 versus Group 1, one month post-first vaccination (Day 30) in HAV-naïve and dengue-naïve participants. Sensitivity analyses were performed on combinations of baseline HAV and dengue serostatus. Secondary objectives included dengue seropositivity one month post-second vaccination (Day 120), HAV geometric mean concentrations (GMCs), and safety.Results900 participants were randomized. On Day 30, HAV seroprotection rates were non-inferior following coadministration of HAV and TAK-003 (Group 3: 98.7 %) to HAV administration alone (Group 1: 97.1 %; difference: ?1.68, 95 % CI: ?8.91 to 4.28). Sensitivity analyses including participants who were neither HAV-naïve nor DENV-naïve at baseline supported this finding. Anti-HAV GMCs on Day 30 were 82.1 (95 % CI: 62.9–107.1) mIU/mL in Group 1 and 93.0 (76.1–113.6) mIU/mL in Group 3. By Day 120, 90.9–96.8 % of TAK-003 recipients were seropositive (neutralizing antibody titer > 10) to all four dengue serotypes. Coadministration of HAV vaccine and TAK-003 was well tolerated, with no important safety risks identified.ConclusionImmune responses following coadministration of HAV vaccine and TAK-003 were non-inferior to administration of HAV vaccine alone. The results support the coadministration of HAV vaccine and TAK-003 with no adverse impact on immunogenicity, safety, and reactogenicity of either vaccine.ClinicalTrials.gov registration: NCT03525119.     

One year safety and immunogenicity of AZD1222 (ChAdOx1 nCoV-19): Final analysis of a randomized,placebo-controlled phase 1/2 trial in Japan

BackgroundLong duration trial data for two-dose COVID-19 vaccines primary series’ are uncommon due to unblinding and additional doses. We report one-year follow-up results from a phase 1/2 trial of AZD1222 (ChAdOx1 nCoV-19) in Japan.MethodsAdults (n = 256) seronegative for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were stratified by age, 18–55 (n = 128), 56–69 (n = 86) and ≥70-year-old (n = 42), and randomized 3:1 to AZD1222 or placebo. Safety, immunogenicity, and exploratory efficacy data were collected until study Day 365.ResultsSafety was consistent with previous reports. In AZD1222 vaccinees, humoral responses against SARS-CoV-2 steadily declined over time. By Day 365, anti-SARS-CoV-2 spike-binding (spike) and receptor-binding domain (RBD) mean antibody titers remained above Day 15 levels and pseudovirus neutralizing antibodies were undetectable in many participants.ConclusionsAZD1222 is immunogenic and well tolerated in Japanese adults. Expected waning in anti-SARS-CoV-2 humoral responses was observed; spike and RBD antibody titers remained elevated. (ClinicalTrials.gov: NCT04568031).     

A phase 2 study of the bivalent VLP norovirus vaccine candidate in older adults; impact of MPL adjuvant or a second dose

IntroductionAcute norovirus gastroenteritis causes significant morbidity and in uncommon cases fatality in older adults. We investigated the safety and immunogenicity of bivalent virus-like particle (VLP) vaccine candidate formulations with and without monophosphoryl lipid A (adjuvant MPL) in this population.MethodsIn this phase II, double-blind, controlled trial 294 healthy adults, ≥ 60 years of age, were randomized (1:1:1:1) to four groups to receive one or two intramuscular immunizations 28 days apart, with 26 18–49 year-old controls who received one MPL-free dose. One-dose groups received placebo on Day 1. Vaccine formulations contained 15 μg GI.1 and 50 μg GII.4c VLP antigens and 500 μg Al(OH)₃, with or without 15 μg MPL. We measured histo-blood group antigen blocking (HBGA) antibodies and ELISA Ig at Days 1, 8, 29, 57, 211 and 393, and avidity indices and cell-mediated immunity (CMI). Solicited local and systemic adverse events (AE) were assessed for 7 days and unsolicited AEs for 28 days after each injection.ResultsAfter one dose HBGA antibodies to both VLP antigens increased with similar kinetics and magnitude in all groups; geometric mean titres (GMTs) persisted above baseline through Day 393. GMTs were similar across age strata (18–49, 60–74, 75–84 and ≥ 85 years of age) and unaffected by a second vaccination or MPL. Total Ig showed similar responses. No clinically relevant differences or changes in avidity or CMI were observed between formulations. Both formulations were well tolerated with no vaccine-related SAEs, the most frequent AEs being mild injection site pain and fatigue.ConclusionsAdults over 60 years of age displayed no safety concerns and had similar immune responses to the norovirus VLP vaccine candidate as younger adults, unaffected by increasing age, a second dose or inclusion of MPL. This data supports the further development of the MPL-free vaccine candidate for older adults.     

CNS demyelinating disease following inactivated or viral vector SARS-CoV-2 vaccines: A case series

BackgroundSeveral reports have been documented in possible association with the administration of different severe acute respiratory coronavirus 2 (SARS-CoV-2) vaccines and central nervous system (CNS)demyelinating disorders, specifically post mRNA vaccines. We report twelve cases of developing Multiple sclerosis (MS) or Neuromyelitis Optica spectrum disorders (NMOSD) following neither the first nor second dose of inactivated or viral vector COVID-19 vaccine.MethodsWe retrospectively compiled twelve patients' medical information with a new onset of MS or NMOSD in their first six weeks following a COVID-19 vaccine.ResultsWe report twelve cases of MS (n = 9), clinically isolated syndrome (CIS)(n = 1), and NMOSD (n = 2) following COVID-19 inactivated vaccines (n = 11) or viral vector vaccines (n = 1), within some days following either the first (n = 3), second dose (n = 8), or third dose (n = 1). Their median age was 33.3 years, ranging from 19 to 53 years. Ten were women (83 %). All patients fully (n = 5) or partially (n = 2) recovered after receiving 3 doses of Corticosteroids. Common medications were Natalizumab, Teriflunomide, Dimethyl fumarate, and Rituximab. Also, Interferon beta 1-a was administered to one patient with severe symptoms of numbness.ConclusionOur case series identifies the Sinopharm BBIBP-CorV and the AstraZeneca AZD1222 vaccines as potential triggers for CNS demyelinating diseases. Vaccine administration routines are not affected by these rare and coincidental events. However, these manifestations are not deniable and require serious attention. Further investigations are needed to clarify the actual mechanisms and real associations.     

2017—2018年成都地区诺如病毒聚集性疫情病原基因型分析

目的 分析2017—2018年成都地区诺如病毒聚集性疫情中病毒基因型构成情况,为疾病防控工作提供依据。方法 选取2017—2018年诺如病毒聚集性疫情标本,对病毒基因RdRp及VP1区片段测序,构建进化树并进行同源性分析。结果 测序结果显示,68份肛拭子标本中 16.2%(11/68)为GⅠ群(包括GⅠ.2、GⅠ.3和GⅠ.5型),83.8%(57/68)为GⅡ群(包括GⅡ.P16-GⅡ.2、GⅡ.P17-GⅡ.17、GⅡ.P8-GⅡ.8、GⅡ.P12-GⅡ.3、GⅡ.P7-GⅡ.6和GⅡ.P15-GⅡ.15型)。2017年以GⅡ.P16-GⅡ.2型为主;2018年GⅠ群及GⅡ.P17-GⅡ.17型均显著增加,同时检出其他4种基因型。各基因型病毒变异不明显,核苷酸同源性为93.4%~100%。结论 2018年成都地区诺如病毒流行株基因型构成较2017年复杂,可能与聚集性疫情增长有关。应持续监测诺如病毒基因型流行情况,及时掌握病毒变异动态,以期提高疾病防控的预警能力。     

Molecular epidemiology of noroviruses detected in Nepalese children with acute diarrhea between 2005 and 2011: Increase and predominance of minor genotype GII.13

Noroviruses, an important cause of acute gastroenteritis, possess a highly divergent genome which was classified into five genogroups and dozens of genotypes. However, changes in genotype distribution over time were poorly understood, particularly in developing countries. We therefore conducted a molecular epidemiological study which characterized the norovirus strains detected in 4437 Nepalese children with acute diarrhea between November 2005 and January 2011 to gain insight into how their genotypes changed over time. Of the 356 samples positive for noroviruses, 277 (78%) were successfully genotyped into 22 capsid genotypes; GII.4 (n = 113), GII.3 (n = 38) and GII.13 (n = 37) were the majority. Interestingly, GII.13 accounted for only 1.7% (4/230) between 2005 and 2008 (period 1) but increased substantially to 26.2% (33/126) between 2009 and 2011 (period 2). Phylogenetic analysis of the VP1 nucleotide sequences of 35 GII.13 strains indicated that they clustered into two lineages named NPL2008 and NPL2009 to which two period 1 strains and 33 period 2 strains belonged, respectively. Lineage NPL2009 contained GII.13 strains that were detected in a large-scale gastroenteritis outbreak in Germany in 2012. Both Nepalese and German VP1 sequences carried two substitutions, H378N and V394Q, in the putative histo-blood group antigen (HBGA)-binding sites. As to the polymerase genotypes of Nepalese strains, the period 1 strains possessed GII.Pm, but the period 2 strains possessed GII.P13, GII.P16, and GII.P21. Together with recent reports on the predominance of GII.P13/GII.13 and GII.P16/GII.13 in India and GII.P16/GII.13 in European countries, this study predicts that genotype GII.13 which was previously regarded as a minor genotype has a potential to become an epidemiologically important genotype.     

Occurrence of Norovirus GII.4 Sydney Variant-related Outbreaks in Korea

Human noroviruses are major causative agents of food and waterborne outbreaks of nonbacterial acute gastroenteritis. In this study, we report the epidemiological features of three outbreak cases of norovirus in Korea, and we describe the clinical symptoms and distribution of the causative genotypes. The incidence rates of the three outbreaks were 16.24% (326/2,007), 4.1% (27/656), and 16.8% (36/214), respectively. The patients in these three outbreaks were affected by acute gastroenteritis. These schools were provided unheated food from the same manufacturing company. Two genotypes (GII.3 and GII.4) of the norovirus were detected in these cases. Among them, major causative strains of GII.4 (Hu-jeju-47-2007KR-like) were identified in patients, food handlers, and groundwater from the manufacturing company of the unheated food. In the GII.4 (Hu-jeju-47-2007KR-like) strain of the norovirus, the nucleotide sequences were identical and identified as the GII.4 Sydney variant. Our data suggests that the combined epidemiological and laboratory results were closely related, and the causative pathogen was the GII.4 Sydney variant strain from contaminated groundwater.