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J Joensuu

Publications and source records attributed to J Joensuu.

14 recordsLinked to original sources

Conserved regions in the sequence of the F4 (K88) fimbrial adhesin FaeG suggest a donor strand mechanism in F4 assembly.

Oral immunization of newly weaned piglets with recombinant F4 (K88) fimbrial adhesin FaeG induces a F4-specific immune response, significantly reducing F4+ Escherichia coli excretion following challenge. In order to use FaeG subunits in an oral vaccine against F4+ enterotoxigenic E. coli, it is necessary to determine the conservation of the adhesin subunit. Hereto, the faeG sequence was determined of 21 F4ac+ E. coli field isolates from piglets with diarrhoea and subsequently compared with these of the reference strain GIS26 and previously reported FaeG sequences from F4ab, F4ac and F4ad antigenic variant strains. The FaeG amino acid sequence was 96-100% homologous within each F4 serotype, but only 92 and 88% when the F4ab and F4ad antigenic variants were compared with the F4ac antigenic variant. Furthermore, the conserved regions of the adhesin suggest a donor strand mechanism in F4 fimbriae assembly as reported for type 1 and P pili. In conclusion, the results of the reported experiments support the usefulness FaeG in an oral subunit vaccine against F4+ E. coli infections or as a mucosal carrier since the adhesin is conserved among F4+ E. coli field isolates.

Adhesins, Escherichia coli↗

Rotaviruses detected by reverse transcription polymerase chain reaction in acute gastroenteritis during a trial of rhesus-human reassortant rotavirus tetravalent vaccine: implications for vaccine efficacy analysis.

BACKGROUND: Rotaviruses are routinely diagnosed by detection of rotavirus antigen in stools using an enzyme immunoassay (EIA). A sensitive method, like reverse transcription polymerase chain reaction (RT-PCR), may reveal more rotaviruses, but the clinical significance of such findings is not well established. OBJECTIVES: To study whether RT-PCR can detect more episodes of rotavirus-associated gastroenteritis than EIA and to determine how rotavirus RT-PCR findings might change efficacy analysis of a rotavirus vaccine trial, in which the outcome measure was rotavirus gastroenteritis diagnosis with EIA. STUDY DESIGN: We applied RT-PCR for detection of rotaviruses in gastroenteritis episodes encountered in an efficacy trial of rhesus-human reassortant rotavirus tetravalent (RRV-TV) vaccine, in a total of 2398 infants. During a follow-up, covering two rotavirus epidemic seasons, 256 cases of rotavirus associated gastroenteritis were detected by EIA; 226 were in the primary efficacy analysis period that included children who had received three doses of vaccine or placebo. RESULTS: With RT-PCR, 84 (33%) more cases of rotavirus gastroenteritis were diagnosed than with EIA, 65 of these were in the primary efficacy analysis period. Clinically, cases of rotavirus gastroenteritis diagnosed by RT-PCR were much milder (median severity score 6 on a 20-point scale) than those diagnosed by EIA (median score 11), P < 0.0001. RT-PCR revealed proportionally more G2 and G4 rotaviruses than EIA. G1 rotaviruses detected by RT-PCR were almost equally divided between RRV-TV (25) vaccine and placebo (28) groups, whereas an apparent vaccine protective effect was seen in the distribution of G2 (one in the RRV-TV and eight in the placebo group) and G4 rotaviruses (six in the RRV-TV and 14 in the placebo group). CONCLUSION: RT-PCR is a useful tool in the diagnosis of rotavirus gastroenteritis, particularly for cases associated with other than the epidemiologically dominant G-type. Application of RT-PCR contributes to the overall appraisal of performance of rotavirus vaccine.

Acute Disease↗

Human calicivirus-associated sporadic gastroenteritis in Finnish children less than two years of age followed prospectively during a rotavirus vaccine trial.

BACKGROUND: Human caliciviruses (HuCV) cause outbreaks of gastroenteritis, but their role in sporadic diarrhea in young children is not well-established. METHODS: Children (n = 2398) participating in a trial of oral rhesus-human reassortant rotavirus tetravalent (RRV-TV) vaccine were evaluated from 2 months to 2 years of age. Stool specimens from 1477 episodes of acute gastroenteritis (788 in a placebo and 689 in a RRV-TV vaccine recipient group) were tested for human calicivirus (HuCV) by reverse transcriptase-PCR with the use of broadly reactive primers, and positive results were confirmed by Southern hybridization with probes specific for main genetic clusters of Genogroups I and II of HuCV. RESULTS: HuCV were detected in 158 (20%) and 155 (22%) cases of gastroenteritis in the placebo and RRV-TV vaccine groups, respectively. According to hybridization results, 8% of HuCV were of Genogroup I and 92% were of Genogroup II. The peak season of HuCV gastroenteritis was from November to February. Of the 148 patients with pure HuCV infection in the placebo group, 89% had vomiting, 79% had watery diarrhea, 21% had fever, 28% needed oral rehydration and 1.4% were hospitalized. The diarrhea in HuCV gastroenteritis was much less severe than that in rotavirus gastroenteritis, but vomiting was equally severe. There was no effect of RRV-TV vaccine on the frequency or clinical severity of HuCV gastroenteritis. CONCLUSION: HuCVs are second in frequency to rotaviruses as causative agents in acute gastroenteritis in young children in the community.

Caliciviridae↗

Concurrent administration of rhesus rotavirus tetravalent (RRV-TV) vaccine with pentavalent diphtheria-pertussis-tetanus-Haemophilus influenzae beta-inactivated polio and hepatitis B vaccines.

To investigate the incorporation of oral rhesus-human reassortant rotavirus tetravalent (RRV-TV) vaccine into a routine immunization programme, RRV-TV or oral placebo was coadministered with a pentavalent diphtheria-tetanus-whole-cell pertussis-Haemophilus influenzae b (Hib)-inactivated polio vaccine and hepatitis B vaccine following a 3-4-5-mo schedule in a double-blind trial involving 249 infants. Seroconversion rates after 3 doses of rotavirus vaccine were 80% for rotavirus immunoglobulin A (IgA) and 93% for RRV neutralizing antibodies. Rotavirus vaccine did not interfere with the immune responses to diphtheria, tetanus, pertussis, Hib, poliovirus 1, 2 and 3, or hepatitis B. Following the first, second and third doses of vaccine, fever >38 degrees C on the day of vaccination was seen in 31%, 24% and 24%, respectively, with no difference between RRV-TV- and placebo-vaccinated children. This fever was presumably due to the whole-cell pertussis vaccine. Those vaccinees who received concomitant RRV-TV vaccine had another peak of fever around d 4 after the first dose, when 25% of them had fever >38 degrees C and 3% >39 degrees C. It is concluded that RRV-TV rotavirus vaccine can be given concurrently with other childhood immunizations following a 3-4-5-mo vaccination schedule. However, febrile reactions to RRV-TV rotavirus vaccine are common when the first dose is given at the age of 3 mo.

Antibody Formation↗

Economic evaluation of rotavirus vaccinations in Finland: randomized, double-blind, placebo-controlled trial of tetravalent rhesus rotavirus vaccine.

The cost-benefit ratio of tetravalent rhesus rotavirus vaccine (RRV-TV) in Finland for prevention of rotavirus gastroenteritis was assessed in a randomized, double-blind, placebo-controlled trial. Costs related to vaccination, side effects, and gastroenteritis were identified. Children received RRV-TV (n = 1,191) or placebo (n = 1,207) at 2, 3, and 5 months of age with other infant vaccinations. Prospective follow-up averaged 1.0 years per child. An intention-to-treat analysis was performed from the perspective of society. Nine cases of severe rotavirus gastroenteritis occurred in the RRV-TV group, versus 100 in the placebo group (P < .0001); mean cost per vaccinated child was 4 Finnish marks (FIM) in the RRV-TV group, versus 203 FIM in the placebo group. Side effects with related costs occurred after 11% and 7% of doses in the RRV-TV group and placebo group, respectively (P < .001); mean cost per child was 89 FIM vs. 75 FIM. The break-even cost (i.e., net benefit, excluding cost of vaccine) of RRV-TV in prevention of severe rotavirus gastroenteritis was 109 FIM (U.S. $19.60) per child.

Cost-Benefit Analysis↗

Symptoms associated with rhesus-human reassortant rotavirus vaccine in infants.

BACKGROUND: Severe rotavirus gastroenteritis is potentially preventable by oral rhesus-human reassortant tetravalent (RRV-TV) vaccine, which may soon be licensed in the US and Europe. The objective of this study was to evaluate symptoms associated with the high titer RRV-TV vaccine given concurrently with routine childhood immunizations. METHODS: In a randomized placebo-controlled double blind trial of RRV-TV vaccine titer 4 x 10(5) plaque-forming units vs. placebo, 2282 children received all 3 doses of study vaccine between ages 2 and 7 months. Symptoms were followed by parents who also took daily rectal temperatures. RESULTS: On Days 3 to 5 after the first dose of vaccine fever 38.0 degrees C or greater was detected in 387 of 1182 (33%) infants in the RRV-TV vaccine group vs. 27 of 1194 (2.3%) infants in the placebo group (P < 0.001) and fever 39.0 degrees C or greater was detected in 40 (3.4%) and 3 (0.2%) infants in the vaccine and placebo groups, respectively (P < 0.001). Irritability, decreased appetite and abdominal cramping on Days 3 to 5 postvaccination were also more common in the RRV-TV vaccine recipients than in the placebo recipients. One child in the RRV-TV group was hospitalized and 2 more infants seen in the clinic, vs. none in the placebo group, within the 5-day period after the first dose for a reason probably related to the RRV-TV vaccine. After the second and third doses of RRV-TV vaccine, there were only minor differences between the vaccine and placebo recipients in fever on Days 3 to 5 postvaccination. CONCLUSIONS: The first dose of RRV-TV vaccine is associated with a relatively high rate of febrile and other reactions, which may require a physician visit and, rarely, hospitalization.

Abdominal Pain↗

Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus gastroenteritis.

BACKGROUND: Rotavirus is the most common cause of acute childhood gastroenteritis. Vaccination with live oral heterologous rotavirus vaccines may prevent rotavirus gastroenteritis. We assessed the efficacy of rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) against severe rotavirus gastroenteritis in Finnish children in a randomised placebo-controlled double-blind trial. METHODS: Placebo or RRV-TV (titre 4x10(5) plaque-forming units) was given to infants at ages 2, 3, and 5 months. The children were followed up for one or two rotavirus epidemic seasons. The main outcome measure was protection against severe rotavirus gastroenteritis (score > or =11 on a 20-point severity scale). 2398 children were enrolled and received at least one dose of RRV-TV (n=1191) or placebo (n=1207). The primary efficacy analysis was based on children who received three doses of RRV-TV (n=1128) or placebo (n=1145). FINDINGS: 256 episodes of rotavirus gastroenteritis occurred at any time during the study; 65 were among 1191 RRV-TV recipients, and 191 among 1207 placebo recipients (vaccine efficacy 66% [95% CI 55-74]; intention-to-treat analysis). 226 episodes were included in the primary efficacy analysis of fully vaccinated children (54 among 1128 RRV-TV recipients, 172 among 1145 placebo recipients; vaccine efficacy 68% [57-76]). 100 episodes were severe, eight in RRV-TV recipients and 92 in placebo recipients (vaccine efficacy 91% [82-96]). INTERPRETATION: RRV-TV vaccine was highly effective against severe rotavirus gastroenteritis in young children. Incorporation of this vaccine into routine immunisation schedules of infants could reduce severe rotavirus gastroenteritis by 90% and severe gastroenteritis of all causes in young children by 60%.

Diarrhea, Infantile↗

Review of rotavirus vaccine trials in Finland.

Oral rotavirus vaccines, including bovine rotavirus strains RIT 4237 and RIT 4256, rhesus rotavirus (RRV) vaccine, rhesus-human rotavirus vaccine reassortants (D x RRV, DS-1 x RRV, and tetravalent RRV), and human nursery rotavirus strain M37, have been evaluated in 5353 Finnish infants for safety, immunogenicity, and efficacy against rotavirus gastroenteritis. Bovine rotavirus vaccines were nonreactogenic in infants, whereas RRV-based and M37 vaccines were occasionally associated with febrile reactions 2-5 days after vaccination. All vaccines showed dose-dependent immunogenicity. Vaccine efficacy correlated with overall immunogenicity but not with the vaccine virus G serotype. For each vaccine, protective efficacy was better against severe rotavirus disease than against any rotavirus-associated gastroenteritis. Maximal protective efficacy against any rotavirus gastroenteritis in subjects with demonstrable vaccine immunogenicity was approximately 75%. To achieve similar protection in all vaccinees, efforts should be focused on enhancing the immunogenicity of oral rotavirus vaccines.

Animals↗

Improved immunogenicity of oral D x RRV reassortant rotavirus vaccine by Lactobacillus casei GG.

In a search for new strategies to improve oral vaccination, the effect of orally administered Lactobacillus casei strain GG (LGG) in conjunction with D x RRV rhesus-human reassortant live oral rotavirus vaccine was tested in 2-5-month-old infants. Infants who received LGG showed an increased response with regard to rotavirus-specific IgM secreting cells, measured using an ELISPOT technique, on day 8 after vaccination. In infants receiving LGG or placebo, respectively, a rotavirus IgM seroconversion was detected in 26/27 (96%), versus 23/27 (85%) cases (p = 0.15) and rotavirus IgA seroconversion was detected in 26/28 (93%) versus 20/27 (74%) cases (p = 0.05). These findings suggest that LGG has an immunostimulating effect on oral rotavirus vaccination. The clinical significance of LGG-enhanced immune responses to oral vaccines should be further evaluated.

Administration, Oral↗