Kirsti Vainio

Analysis of Integrated Virological and Epidemiological Reports of Norovirus Outbreaks Collected within the Foodborne Viruses in Europe Network from 1 July 2001 to 30 June 2006

ABSTRACT The Foodborne Viruses in Europe network has developed integrated epidemiological and virological outbreak reporting with aggregation and sharing of data through a joint database. We analyzed data from reported outbreaks of norovirus (NoV)-caused gastroenteritis from 13 European countries (July 2001 to July 2006) for trends in time and indications of different epidemiology of genotypes and variants. Of the 13 countries participating in this surveillance network, 11 were capable of collecting integrated epidemiological and virological surveillance data and 10 countries reported outbreaks throughout the entire period. Large differences in the numbers and rates of reported outbreaks per country were observed, reflecting the differences in the focus and coverage of national surveillance systems. GII.4 strains predominated throughout the 5-year surveillance period, but the proportion of outbreaks associated with GII.4 rose remarkably during years in which NoV activity was particularly high. Spring and summer peaks indicated the emergence of genetically distinct variants within GII.4 across Europe and were followed by increased NoV activity during the 2002-2003 and 2004-2005 winter seasons. GII.4 viruses predominated in health care settings and in person-to-person transmission. The consecutive emergence of new GII.4 variants is highly indicative of immune-driven selection. Their predominance in health care settings suggests properties that facilitate transmission in settings with a high concentration of people such as higher virus loads in excreta or a higher incidence of vomiting. Understanding the mechanisms driving the changes in epidemiology and clinical impact of these rapidly evolving RNA viruses is essential to design effective intervention and prevention measures.

Emergence of new norovirus variants on spring cruise ships and prediction of winter epidemics.

In June 2006, reported outbreaks of norovirus on cruise ships suddenly increased; 43 outbreaks occurred on 13 vessels. All outbreaks investigated manifested person-to-person transmission. Detection of a point source was impossible because of limited investigation of initial outbreaks and data sharing. The most probable explanation for these outbreaks is increased norovirus activity in the community, which coincided with the emergence of 2 new GGII.4 variant strains in Europe and the Pacific. As in 2002, a new GGII.4 variant detected in the spring and summer corresponded with high norovirus activity in the subsequent winter. Because outbreaks on cruise ships are likely to occur when new variants circulate, an active reporting system could function as an early warning system. Internationally accepted guidelines are needed for reporting, investigating, and controlling norovirus illness on cruise ships in Europe.

Molecular Epidemiology of Norovirus Outbreaks in Norway during 2000 to 2005 and Comparison of Four Norovirus Real-Time Reverse Transcriptase PCR Assays

ABSTRACT During the period from January 2000 to August 2005 a total of 204 outbreaks of norovirus gastroenteritis were diagnosed at the Norwegian Institute of Public Health. A clear increase in the norovirus activity was seen in healthcare institutions during the winter seasons. Polymerase sequence analysis of norovirus strains from 122 outbreaks showed that 112 were caused by GII strains (91.8%). Two norovirus variants seen during the study period—GIIb and GII.4—were predominant between January 2000 and September 2002, whereas GII.4 was predominant from September 2002 onward. The highest norovirus activity was seen during the 2002-2003 and 2004-2005 seasons with the emergence of new GII.4 variants. This study describes the molecular epidemiology of norovirus strains circulating in Norway during the five previous seasons and compares four norovirus real-time reverse transcriptase PCR assays. A suitable assay for routine diagnostics is suggested.

Two cases of acute severe flaccid myelitis associated with enterovirus D68 infection in children, Norway, autumn 2014

Enterovirus D68 (EV-D68), phylogenetic clade B was identified in nasopharyngeal specimens of two cases of severe acute flaccid myelitis. The cases were six and five years-old and occurred in September and November 2014. EV-D68 is increasingly associated with acute flaccid myelitis in children, most cases being reported in the United States. Awareness of this possible neurological complication of enterovirus D68 infection is needed.

Evaluation of a rapid method for recovery of norovirus and hepatitis A virus from oysters and blue mussels

Foodborne outbreaks caused by noroviruses (NoVs) and hepatitis A virus (HAV) are often linked to consumption of contaminated shellfish. The objective of this study was to identify an appropriate virus recovery method for real-time reverse transcriptase (RT)-PCR detection and subsequently to evaluate this method on shellfish bioaccumulated with virus in a collaborative study. Five methods were compared for recovery of NoV GII.7 and feline calicivirus from spiked digestive tissue of oysters and mussels. A method based on proteinase K digestion followed by NucliSENS miniMAG extraction was found to be the most efficient with a 50% limit of detection (LOD(50)) of 62 and 12 RT-PCR U/1.5 g digestive tissue for NoV GII.7 in oysters and mussels, respectively. Evaluation of the method in four laboratories found the percentage of sensitivity, based on low/high levels of virus bioaccumulated in oysters, to be 33/80 for NoV GI.3b, 13/92 for NoV GII.4 and 50/42 for HAV. A specificity of 100% was found for all three viruses in non-bioaccumulated oysters. As process control Mengovirus (vMC(0)) showed an average recovery of 1.8% from oysters and 1.2% from mussels. The study demonstrates that this recovery method can be useful for harmonized data generation and routine viral analyses of shellfish.

Prenatal exposure to polychlorinated biphenyls and dioxins from the maternal diet may be associated with immunosuppressive effects that persist into early childhood.

We investigated whether prenatal exposure from the maternal diet to the toxicants polychlorinated biphenyls (PCBs) and dioxins is associated with the development of immune-related diseases in childhood. Children participating in BraMat, a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa), were followed in the three first years of life using annual questionnaires (0-3years; n=162, 2-3years; n=180), and blood parameters were examined at three years of age (n=114). The maternal intake of the toxicants was calculated using a validated food frequency questionnaire from MoBa. Maternal exposure to PCBs and dioxins was found to be associated with an increased risk of wheeze and more frequent upper respiratory tract infections. Furthermore, maternal exposure to PCBs and dioxins was found to be associated with reduced antibody response to a measles vaccine. No associations were found between prenatal exposure and immunophenotype data, allergic sensitization and vaccine-induced antibody responses other than measles. Our results suggest that prenatal dietary exposure to PCBs and dioxins may increase the risk of wheeze and the susceptibility to infectious diseases in early childhood.

Effect of withholding breastfeeding on the immune response to a live oral rotavirus vaccine in North Indian infants

Interference from transplacental and breast milk antibodies may impede the performance of oral live vaccines. The effect of breastfeeding on the immunogenicity of Rotarix, a two-dose oral monovalent rotavirus vaccine, was examined in a community-based trial in New Delhi, India. Four hundred mother-infant pairs were randomized into two equal groups. Infants were aged 6-7 weeks at enrollment. Mothers were encouraged to either breastfeed or to withhold breastfeeding during the 30 min prior to and after each vaccine dose was administered. We collected blood specimens from infants at enrollment and 4 weeks after the second vaccine dose. Blood and breast milk specimens were obtained from mothers at baseline and breast milk specimens were collected at the time of the second vaccine dose. Seroconversion was defined as infant serum anti-VP6 IgA antibody level of ≥20 IU/mL 4 weeks after the second vaccine dose and a ≥4-fold rise from baseline. There was no difference in the proportion who seroconverted between the two groups (26% vs 27%; p=0.92). The levels of infant serum IgA, maternal serum and breast milk IgA and IgG anti-rotavirus antibodies predicted the anti-rotavirus IgA level in infants at end-study and explained approximately 10% of the variability of the immune response (r(2)=0.10, p<0.001). In this population, the immune response to Rotarix was not enhanced by withholding breastfeeding around the time of vaccination. Maternal anti-rotavirus antibodies explained little of the variability in the immune response to the vaccine. Factors other than maternal anti-rotavirus antibodies probably explain why infants in low-and middle-income settings respond poorly to live oral rotavirus vaccines.

Susceptibility to cytomegalovirus, parvovirus B19 and age-dependent differences in levels of rubella antibodies among pregnant women

Infections caused by cytomegalovirus (CMV), parvovirus B19 (B19), and rubella can lead to serious complications in pregnant women. The aim of this study was to determine the susceptibility to CMV, B19, and rubella antibodies in pregnant women in Norway. Consecutive sera samples were collected from pregnant women in two different regions in Norway. Sera were collected from age groups; ≤19, 20–24, 25–29, 30–34, 35–39, and ≥40 years old. Of the 2,000 pregnant women tested, anti‐CMV IgG was positive in 62.8% anti‐parvovirus B19 IgG in 59.7% and anti‐rubella IgG in 94.4%. CMV IgG susceptibility has decreased in pregnant women less than 30 years of age, from 60% in a study conducted in 1973–1974 to 37.2% in present study. There was a significant difference in CMV IgG seropositivity rate between the two regions (58.6% and 67.1%). Serum levels of rubella IgG was lowest in age group 25–29 years with a positivity rate of 91.0%. Women born before vaccination with two doses of MMR started, had both a higher positivity rate and significantly higher levels of rubella antibody titre, 96.1% and 82.2 IU/ml compared to those born after 92.9% and 41.7 IU/ml. Significantly lower anti‐rubella IgG titre found in the youngest age groups highlights the need for continued antenatal screening. A considerable increase in anti‐CMV‐IgG seropositivity rate was observed and might be associated with higher rate of breastfeeding and a higher percentage attending day‐care centres. J. Med. Virol. 86:820–826, 2014.

Interference between outbreaks of epidemic viruses

Dear Sir, It has been observed that epidemic respiratory viruses such as influenza virus and respiratory syncytial virus (RSV) usually do not reach their epidemic peaks during the same period [1 4]. A reasonable explanation for this finding could be that elevated levels of cytokines in the population during influenza epidemic periods could have an additive effect on the herd immunity of other respiratory viruses, in particular RSV [2 5]. On the other hand, epidemic gastroenteritis viruses such as norovirus possess several entities in common with influenza virus:

Detection of measles- and mumps-specific IgG antibodies in paired serum and oral fluid samples from Norwegian conscripts

The aim of this study was to measure the seroprevalence to mumps in Norwegian conscripts belonging to the first children vaccination cohorts that had been offered two doses of MMR vaccine. The seroprevalence to mumps was 76% with the Microimmune assay and 85% with the Enzygnost assay. We also compared the performance of the Microimmune assay for detection of mumps- and measles-specific IgG antibodies in 340 paired serum and oral fluid samples from the conscripts and evaluated the effect of revaccination. Mumps-specific IgG antibodies were detected in only 61% of the oral fluids. In contrast, high levels of measles-specific IgG antibodies were detected in both the serum and oral fluid samples. Based on these results, we are only able to recommend the use of oral fluid for surveillance of measles in Norway. Our results may also indicate that the seroprevalence necessary to interrupt transmission of mumps has not been reached in vaccinated young adult Norwegians. Seroconversion was observed in all initially measles seronegative conscripts after revaccination, whereas 23 of 27 initially mumps seronegative conscripts failed to seroconvert.