Assessment of Food and Waterborne Viral Outbreaks by Using Field Epidemiologic, Modern Laboratory and Statistical Methods-Lessons Learnt from Seven Major Norovirus Outbreaks in Finland.

Seven major food- and waterborne norovirus outbreaks in Western Finland during 2014-2018 were re-analysed. The aim was to assess the effectiveness of outbreak investigation tools and evaluate the Kaplan criteria. We summarised epidemiological and microbiological findings from seven outbreaks. To evaluate the Kaplan criteria, a one-stage meta-analysis of data from seven cohort studies was performed. The case was defined as a person attending an implicated function with diarrhoea, vomiting or two other symptoms. Altogether, 22% (386/1794) of persons met the case definition. Overall adjusted, 73% of norovirus patients were vomiting, the mean incubation period was 44 h (4 h to 4 days) and the median duration of illness was 46 h. As vomiting was a more common symptom in children (96%, 143/149) and diarrhoea among the elderly (92%, 24/26), symptom and age presentation should drive hypothesis formulation. The Kaplan criteria were useful in initial outbreak assessments prior to faecal results. Rapid food control inspections enabled evidence-based, public-health-driven risk assessments. This led to probability-based vehicle identification and aided in resolving the outbreak event mechanism rather than implementing potentially ineffective, large-scale public health actions such as the withdrawal of extensive food lots. Asymptomatic food handlers should be ideally withdrawn from high-risk work for five days instead of the current two days. Food and environmental samples often remain negative with norovirus, highlighting the importance of research collaborations. Electronic questionnaire and open-source novel statistical programmes provided time and resource savings. The public health approach proved useful within the environmental health area with shoe leather field epidemiology, combined with statistical analysis and mathematical reasoning.

Shopping Detail Information and Home Freezer Sampling Confirmed the Role of Commercial, Modified-Atmosphere Packaged Meatballs as a Vehicle for Listeriosis in Finland.

In November 2016, an elderly patient was diagnosed with Listeria monocytogenes bacteremia in Finland. Grocery store loyalty card records and microbiological investigation of foods found in the home fridge and freezer of the patient revealed commercial, modified-atmosphere packaged meatballs as the source of the infection. Investigation of the meatball production plant revealed that the floor drain samples were contaminated with the same L. monocytogenes strain as those isolated from the patient and meatballs. Ready-to-eat meatballs were likely contaminated after heat treatment from the production environment before packaging. Long-term cold storage, modified-atmosphere conditions, and the absence of competing bacteria presumably enhanced the growth of L. monocytogenes. We recommend that collection of shopping details and home fridge and freezer sampling should be part of surveillance of all cases of L. monocytogenes infections to complement information obtained from in-depth interviews.

An Outbreak of Norovirus Infections Among Lunch Customers at a Restaurant, Tampere, Finland, 2015.

On January 29, 2015, the city of Tampere environmental health officers were informed of a possible foodborne outbreak among customers who had eaten lunch in restaurant X. Employees of electric companies A and B had a sudden onset of gastrointestinal symptoms. We conducted a retrospective cohort study to identify the vehicle, source, and causative agent of the outbreak. A case was defined as an employee of companies A or B with diarrhea and/or vomiting who ate lunch at Restaurant X on January 26, 2015. All employees of the companies attending the implicated lunch were invited to participate in the cohort study. Environmental investigation was conducted. Twenty-one responders were included in statistical analysis, of which 11 met with the case definition. Of the 15 food items consumed by participants, four food items were associated with gastroenteritis. Of four kitchen staff, three tested positive for norovirus GIP7, the strain was found earlier in the community. No patient samples were obtained. Level of hygiene in the kitchen was inadequate. Infected kitchen staff probably transmitted norovirus by inadequate hygiene practices. No new cases associated with Restaurant X were reported after the hygiene practices were improved.

Rotavirus antigenemia in children is associated with more severe clinical manifestations of acute gastroenteritis.

BACKGROUND: Rotavirus (RV) antigenemia and RNAemia are common findings in rotavirus-infected children. Sporadic associations between RV antigenemia and extraintestinal manifestations of RV infection have been observed. We examined the clinical severity of RV gastroenteritis in patients with and without RV antigenemia or RNAemia. METHODS: Stool, serum and whole blood samples were collected from children seen with acute gastroenteritis in Tampere University Hospital and studied for RV using reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Only exclusively RV-positive specimens were included into this study. The patients were divided into groups according to RV findings from stool, serum and blood specimens. Clinical manifestations were graded according to 20-point Vesikari scoring system. RESULTS: Of 374 children, 155 (41%) had RV in their stools. Of these 155 children, 105 (67%) were found to have RV RNA in the serum; of those, 94 (90%) had also RV enzyme-linked immunosorbent assay antigen. Thus antigenemia occurred in 61% (94 cases) of RV-infected children all of whom had concomitant RNAemia. Neither antigenemia nor RNAemia were detected in 85 patients with non-RV gastroenteritis. Patients who had RV RNA and RV antigen in both serum and stools were more likely to have a higher level of fever and more severe vomiting than patients who had RV only in stools. G1 genogroup RV was more often associated with RNAemia and antigenemia than other genogroups combined. CONCLUSION: Rotavirus antigenemia and viremia are commonly detected in children hospitalized for RV gastroenteritis and may be associated with increased severity of fever and vomiting.

Major reduction of rotavirus, but not norovirus, gastroenteritis in children seen in hospital after the introduction of RotaTeq vaccine into the National Immunization Programme in Finland.

UNLABELLED: Universal rotavirus (RV) vaccination is expected to reduce hospitalizations for acute gastroenteritis (GE) of children by eliminating most of severe RVGE, but it does not have any effect on norovirus (NV), the second most common causative agent of GE in children. After the introduction of the RV vaccine into the National Immunization Programme (NIP) of Finland in 2009, we conducted a prospective 2-year survey of GE in children seen in Tampere University Hospital either as outpatients or inpatients and compared the results with a similar 2-year survey conducted prior to NIP in the years 2006-2008. Compared with the pre-NIP 2-year period, in 2009-2011, hospitalizations for RVGE were reduced by 76 % and outpatient clinic visits were reduced by 81 %. NVGE showed a slight decreasing trend and accounted for 34 % of all cases of GE seen in hospital in pursuance of RVGE having decreased to 26 % (down from 52 %). In cases admitted to the hospital ward, RV accounted for 28 % and NV accounted for 37 %.The impact of RV vaccination was reflected as a 57 % decrease in all hospital admissions and 62 % decrease in all outpatient clinic visits for GE of any cause. CONCLUSION: RV vaccination in NIP has led to a major reduction of hospital admissions and clinic visits due to RVGE, but has had no effect on NVGE. After 2 years of NIP, NV has become the leading cause of acute GE in children seen in hospital.

Human bocavirus types 1, 2 and 3 in acute gastroenteritis of childhood.

AIM: Recently identified human bocavirus (HBoV) types 2 and 3 have been associated with acute gastroenteritis in children. We studied 878 stool specimens from children with acute gastroenteritis and 112 controls (43 children with unspecified fever, 33 with respiratory tract infection and 36 healthy children) for known HBoVs. The same specimens were previously studied for rotaviruses, noroviruses, sapoviruses, adenoviruses, coronaviruses and aichivirus. METHODS: HBoVs were detected by PCR and positive amplicons were sequenced to identify HBoV1, HBoV2, HBoV3 and HBoV4. RESULTS: HBoV of any type was found in 85 (9.7%) cases of acute gastroenteritis and in 6 (5.4%) controls. HBoV1 was detected in 49 (5.6%) cases and 2 (1.8%) controls, HBoV2 in 29 (3.3%) cases and 2 (1.8%) controls and HBoV3 in 8 (0.9%) cases and 2 (1.8%) controls. No HBoV4 was found. HBoV as a single infection was found in 16 (1.8%) cases and in 6 (5.4%) controls; in the remaining cases, a known gastroenteritis virus was also found. Among the single HBoV infections, HBoV2 was the most common type with 8 (50%) cases. CONCLUSION: HBoVs are rarely found alone in children with acute gastroenteritis. Further studies are warranted to confirm a possible specific association of HBoV2 with gastroenteritis.

Simultaneous presence of human herpesvirus 6 and adenovirus infections in intestinal intussusception of young children.

AIM: This prospective study investigated the role of viral infections in the pathogenesis of intussusception, including human herpesvirus 6 (HHV-6), a known lymphotropic virus. METHODS: Fifty-three children with intussusception treated in hospital were enroled, and children of comparable age and gender served as controls. Blood, stool and throat swab specimens, as well as mesenteric lymph nodes and pieces of intestine from patients requiring surgery were tested for various viruses by PCR methods. RESULTS: Altogether, 85% of intussusception cases showed evidence of a recent or ongoing viral infection. Among the 53 intussusception cases, adenovirus was detected in 25 (47%), HHV-6 in 24 (45%), rhinovirus in 12 (23%), cytomegalovirus in 7 (13%), enterovirus in 4 (8%) and rotavirus in 3 (6%) patients. Of the 50 whole blood samples, 44% were positive for HHV-6 and of the 16 resected mesenteric lymph nodes, 50% were positive for HHV-6. Simultaneous presence of HHV-6 and adenovirus infection correlated significantly with intussusception (OR 12.1, 95% CI 2.2 to 66.5). CONCLUSIONS: A statistically significant association was observed between adenovirus and childhood intussusception. HHV-6 was a common finding and occurred concomitantly with other viruses. A simultaneous infection with HHV-6 and adenovirus carried the highest risk for intussusception.

Noroviruses as a major cause of acute gastroenteritis in children in Finland, 2009-2010.

Noroviruses are, after rotaviruses, the second most common cause of acute gastroenteritis in young children. In a prospective study conducted in 2009-2010 at the Tampere University Hospital, 195 stool specimens were collected from cases of acute gastroenteritis in children and examined for noroviruses, sapoviruses, and rotaviruses, using a reverse transcriptase polymerase chain reaction (RT-PCR). Noroviruses were found in 49 (25%) of the cases and sapoviruses in 12 (6%). The norovirus genotype GII.4 dominated with a 76% share; other genotypes detected were GII.7/GII.6 (16%), GII.g/GII.12, GII.e/GII.4, and GII.7 (2% each). For comparison, 47 (24%) cases of rotavirus gastroenteritis were diagnosed in the same period. In conclusion, after the introduction of rotavirus vaccination in Finland in September 2009, noroviruses have become as common as rotaviruses as the causative agents of acute gastroenteritis in young children, and are likely to become the leading cause. Norovirus GII.4 continues to be the dominant genotype.

Noroviruses in children seen in a hospital for acute gastroenteritis in Finland.

UNLABELLED: Noroviruses (NoVs) are second only to rotaviruses (RVs) as causative agents of acute gastroenteritis (AGE) in children. The proportional role of NoVs is likely to increase after control of RV by vaccination. We investigated NoVs in children seen in Tampere University Hospital either treated as outpatients or hospitalized because of AGE before universal RV vaccination was implemented in Finland. This prospective study was conducted from September 2006 to August 2008. A total of 1,128 children <15 years of age with symptoms of AGE were enrolled either in the hospital clinic or in a ward, and stool samples for NoV studies were obtained from 759 children. NoVs were found in 196 (26%) cases. In the first year, NoVs were found in 116 (34%) out of 341, and in the second year, in 80 (19%) out of 418 cases. RVs were found respectively in 128 (38%) and 260 (62%) cases in these two seasons. Both RV and NoV were present in 24 cases. NoV genotype GII.4 predominated with a 96% share of the NoV cases in the first season and an 80% share in the second season. Other NoV genotypes seen infrequently were GII.7, GIIb, GI.6, GII.1, GII.2, and GIIc. The median clinical severity of NoV AGE was 14 compared to 16 for RV AGE on a 20-point scale. CONCLUSION: NoVs were nearly as common as RVs as causative agents of severe AGE in children seen in hospital. After implementing universal RV vaccination, the importance of NoVs will still increase further.

Rotavirus gastroenteritis in Finnish children in 2006-2008, at the introduction of rotavirus vaccination.

Rotaviruses (RV) are major causative agents of acute gastroenteritis (AGE) requiring hospitalization in children; RV hospitalizations may be largely eliminated by universal mass vaccination with RV vaccine. We conducted a hospital-based prospective survey of AGE in children over 2 RV epidemic seasons, from 2006 to 2008, when the coverage of RV vaccination in Finland increased to 35% of the birth cohort. RVs were detected by reverse transcription polymerase chain reaction (RT-PCR). In the first season, only 38% of AGE cases were RV-positive, and the onset of the RV season was delayed. Type G1P[8], RVs accounted for 40%, G2P[4] for 19%, G3P[8] for 2%, G4P[8] for 2% and G9P[8] for 38%. In the second season, 63% of AGE cases were RV-positive: G1P[8] accounted for 73%, G2P[4] for only 3%, G3P[8] for 4%, G4P[8] for 13%, and G9P[8] had almost disappeared. G2P[4] RV did not become predominant at the coverage level of 29% of G1P[8] human RV vaccine. RV-associated hospitalizations were seen in children up to the age of 9 y. This study forms the epidemiological background for the follow-up of the impact of universal RV vaccination in Finland introduced in 2009.

Detection of human coronaviruses in children with acute gastroenteritis.

BACKGROUND: Human coronaviruses (HCoVs) are known respiratory pathogens. Moreover, coronavirus-like particles have been seen by electron microscope in stools, and SARS-HCoV has been isolated from intestinal tissue and detected in stool samples. OBJECTIVES: To find out if HCoVs can be found in stools of children with acute gastroenteritis and to assess the significance of HCoVs in the etiology of acute gastroenteritis in children. STUDY DESIGN: 878 stool specimens from children with acute gastroenteritis and 112 from control children were tested by RT-PCR to detect HCoV groups 1B, 2A and SARS. HCoVs were typed by sequencing all PCR positive samples. RESULTS: Twenty-two (2.5%) of the 878 stool specimens of children with acute gastroenteritis were positive for HCoVs. The following HCoV types were detected: OC43 (10 cases, 45.5%), HKU1 (6 cases, 27.3%), 229E (2 cases, 9.1%) and NL63 (4 cases, 18.2%). In 4 of the cases a HCoV was the only detected virus; in the remaining cases rotavirus or norovirus was found in the same sample. In control groups there were two HCoV positive samples of 112 tested. CONCLUSIONS: This study shows that all known non-SARS HCoVs can be found in stools of children with acute gastroenteritis. On the basis of this study, the significance of coronaviruses as gastrointestinal pathogens in children appears minor, since most of the coronavirus findings were co-infections with known gastroenteritis viruses.