Multiple norovirus outbreaks among workplace canteen users in Finland, July 2006.

Multiple gastroenteritis outbreaks occurred between 25 and 31 July 2006 in 10 workplace canteens in south-western Finland. One vegetable processing plant provided raw vegetables to all the canteens. We conducted cohort studies in the three most visited canteens and environmental investigations in the kitchens and the plant. Patients' stools, food, water and environmental samples were tested for enteric bacteria and viruses. Of the three canteens, 150/273 respondents (response rate 82%) had gastroenteritis. Consumption of mixed raw vegetables was significantly associated with the illness but no single vegetable explains the outbreak. An identical norovirus GII.1 genotype was detected from all genotyped patient samples. Water, food, and environmental samples were negative for norovirus. The facilities had appropriate hygienic conditions and no staff member had gastroenteritis prior to the outbreak. Tracing back the vegetables to the farm level proved unsuccessful. This was the largest foodborne norovirus outbreak in Finland.

Immune responses to pertussis antigens eight years after booster immunization with acellular vaccines in adults.

Pertussis-specific antibody and cell-mediated immune (CMI) responses were studied in adults 8 years after booster immunization with either a bicomponent (pertussis toxin and filamentous hemagglutinin) or a monocomponent (pertactin) acellular vaccine and in age-matched healthy controls. The levels of vaccine-induced antibodies were also compared between the serum samples collected before, 1 month, 4 years, and 8 years after immunization. Over the follow-up period, geometric mean values (GMV) of antibodies to the vaccine antigens decreased in both groups of vaccinees. However, the 8-year postimmunization GMV were 3-20 times higher than preimmunization GMV (all P values <0.01). Moreover, both antibody and CMI responses to the vaccine antigens were significantly higher in the vaccinees than in the controls (all P<0.01 for antibody; all P<0.001 for CMI responses). The results show that antibody and CMI responses induced by acellular pertussis vaccines can persist for up to 8 years after booster immunization of adults primed with whole-cell vaccine.

Acellular vaccines containing reduced quantities of pertussis antigens as a booster in adolescents.

OBJECTIVE: To evaluate the immunogenicity and reactogenicity of an acellular pertussis vaccine (pa) either formulated with diphtheria and tetanus toxoids (dTpa) or administered consecutively with a licensed tetanus and diphtheria vaccine (Td) as a 5th dose in adolescents. METHODS: A total of 510 healthy children 10 to 13 years of age were assigned randomly, using a single-blind design, to receive either the dTpa vaccine or the Td vaccine with the pa vaccine 1 month later. The quantities of 3 pertussis antigens (pertussis toxin, filamentous hemagglutinin, and pertactin) in the dTpa and the pa vaccines were one third of those of the Infanrix vaccine (SmithKline Beecham Biologicals, Rixensart, Beligium) licensed for use in infants. For enzyme-linked immunosorbent assay measurement of serum immunoglobulin G antibodies and proliferation assay of peripheral blood mononuclear cells, blood samples were obtained before and 1 month after immunization. Local and systemic reactions were recorded on diary cards for 15 days after immunization. RESULTS: After immunization with dTpa or pa, significant and comparable rises in geometric mean values of antibodies (12- to 46-fold) and proliferations (8- to 18-fold) to each of the pertussis antigens were noted. After immunization with dTpa or Td, significant rises in geometric mean values of antidiphtheria and antitetanus antibodies (35- to 76-fold) were noted, and all subjects had values of these antibodies >/=.1 international units/mL. The dTpa and pa vaccines were at least as well tolerated as the licensed Td vaccine. CONCLUSIONS: Booster immunization of adolescents with an acellular vaccine containing reduced quantities of pertussis antigens in addition to diphtheria and tetanus toxoids induces good responses in both arms of the immune system without an increase in adverse reactions.

Cell-mediated immune responses to antigens of Bordetella pertussis and protection against pertussis in school children.

BACKGROUND: Increasing evidence suggests that cell-mediated immunity (CMI) is involved in immune response against Bordetella pertussis. However, there are practically no studies evaluating the significance of pertussis-specific CMI in relation to protection against clinical pertussis. METHODS: An outbreak of pertussis was studied prospectively in 13-year-old pupils in a rural school. B. pertussis infection was diagnosed by culture, microagglutination and enzyme immunoassay serology with the use of pertussis toxin, filamentous hemagglutinin and pertactin as antigens. Pertussis-specific CMI responses were assessed by in vitro proliferation assay of peripheral blood mononuclear cells. RESULTS: At the initial sampling 7 of 22 children had symptoms suggestive of pertussis and 15 were asymptomatic. Of the latter 3 remained healthy, 8 were later confirmed to have had asymptomatic infection, 3 developed laboratory-confirmed pertussis and 1 developed cough without laboratory evidence of pertussis. Initial in vitro proliferations of peripheral blood mononuclear cells induced by pertussis toxin, filamentous hemagglutinin and/or pertactin were positive in all 3 healthy children, in 6 of 8 children who had asymptomatic infection, but in none of the 3 children who later developed pertussis. Although some children who remained healthy had high values of antibodies, no clear association was found between initial serum antibody values and clinical outcome. CONCLUSIONS: These preliminary data suggest that CMI may have an important role in protection against clinical pertussis but do not exclude a role for antibodies. Furthermore the results stress a multifactorial nature of the immune protection against B. pertussis.

Antibody and cell-mediated immune responses to booster immunization with a new acellular pertussis vaccine in school children.

235 healthy 10-12 years old school children were randomly immunized with either a booster dose of diphtheria-tetanus-acellular pertussis (dTap) or diphtheria-tetanus (dT) vaccine. For this booster immunization designed for school children and adults, the quantities of Bordetella pertussis antigens in the dTap vaccine had been reduced to one third of those of the Infanrix vaccine (SmithKline Beecham) commonly used for infants. IgG antibodies and cell-mediated immune (CMI) responses to pertussis toxin (PT), pertactin (PRN) and filamentous hemagglutinin (FHA) were assessed by an enzyme immunosorbent assay and in vitro proliferation of peripheral blood mononuclear cells, respectively. Before immunization, 55%, 80% and 99% of children had detectable serum IgG antibodies to PT, PRN and FHA, whereas CMI response was found in 35%, 27% and 50% of children, respectively. After immunization, a 20-30-fold increase in geometric mean level (GML) of antibodies to the pertussis antigens occurred and CMI response to PT, PRN and FHA was seen in 88%, 94% and 100% of children, respectively. Adverse reactions following the immunization were rare. The results show that booster immunization with an acellular pertussis vaccine with reduced concentrations of antigens induces both antibody and CMI responses and support further studies of this pertussis vaccine in school children.

Cytokine mRNA expression and proliferative responses induced by pertussis toxin, filamentous hemagglutinin, and pertactin of Bordetella pertussis in the peripheral blood mononuclear cells of infected and immunized schoolchildren and adults.

Pertussis infection is increasingly recognized in older children and adults, indicating the need of booster immunizations in these age groups. We investigated the induction of pertussis-specific immunity in schoolchildren and adults after booster immunization and natural infection. The expression of mRNA of gamma interferon (IFN-gamma), interleukin-2 (IL-2), IL-4, and IL-5 in the peripheral blood mononuclear cells (PBMCs) was assayed by reverse transcription-PCR. The PBMCs of 17 children immunized with one dose of an acellular vaccine containing pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) significantly proliferated in vitro after stimulation with the vaccine antigens. The PBMCs of seven infected individuals markedly proliferated in the presence of PT and FHA, but the cells of only two of these subjects responded to PRN. At least one of the antigens induced mRNA for IL-4 and/or IL-5 in the cells of 93% of tested vaccinees and patients, and FHA induced IFN-gamma mRNA in the cells of two-thirds of them. Expression of mRNA for IFN-gamma correlated with the production of the cytokine protein. Anti-FHA immunoglobulin G antibodies significantly correlated with FHA-induced proliferative responses both before and after immunization. These results show that booster immunization with acellular pertussis vaccine induces both antibody- and cell-mediated immune responses in schoolchildren. Further, booster immunization and natural infection seem to induce the expression of mRNA of T-helper 1 (Th1) and Th2 type cytokines in similar manners. This observation supports the use of acellular pertussis vaccines for booster immunizations of older children, adolescents, and adults.

Islet cell and glutamic acid decarboxylase antibodies and heat-shock protein 65 responses in children with newly diagnosed insulin-dependent diabetes mellitus.

Islet cell antibodies (ICA) were detected in 66% and glutamic acid decarboxylase (GAD) antibodies in 64% of children (n = 47) with newly diagnosed insulin-dependent diabetes mellitus (IDDM). Fifteen percent of the patients had neither GAD nor ICA antibodies. Responses to mycobacterial heat-shock protein 65 (Hsp65) were detected in all patients. There was a significant correlation between anti-GAD antibodies and proliferation of peripheral blood mononuclear cells to Hsp65, and between ICA and antibodies to Hsp65.