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T Vesikari

Publications and source records attributed to T Vesikari.

At least 19 recordsLinked to original sources

Screening of rotavirus and adenovirus infections during prolonged hospitalization in a neonatal unit.

UNLABELLED: Rotavirus and adenovirus infections in 308 infants hospitalized for longer than 1 wk, and cases with necrotizing enterocolitis, were screened in a neonatal unit during a 15 mo period, covering two rotavirus epidemics in the community. Altogether, 1020 stool samples were collected weekly until hospital discharge, and in necrotizing enterocolitis cases at the onset of symptoms, and tested for rotavirus and adenovirus by means of enzyme-linked immunosorbent assay. The positive samples were further analysed by polymerase chain reaction. Enzyme-linked immunosorbent assay revealed five adenovirus-positive cases, which were tested negative by polymerase chain reaction. Out of 16 necrotizing enterocolitis cases, one was adenovirus- and another rotavirus positive when tested by polymerase chain reaction, the latter having a concomitant Candida albicans septicaemia. CONCLUSION: Routine rotavirus and adenovirus screening in hospitalized neonates seems to be unnecessary. Viral diagnostic examinations should be considered in patients with necrotizing enterocolitis.

Adenoviridae Infections↗

Effect of rotavirus vaccine on Sapporo virus gastroenteritis in Finnish infants.

BACKGROUND: Sapporo-like viruses (SLVs) occur worldwide, but there is limited information about the SLV-associated gastroenteritis outside Japan. METHODS: Stool specimens from 1,432 episodes of gastroenteritis that occurred in children between 2 months and 2 years of age during a rotavirus vaccine trial (776 episodes in placebo-vaccinated and 656 in rotavirus-vaccinated infants) were examined for SLVs using a reverse transcription-PCR assay. The reverse transcription-PCR took advantage of new primers specific for Sapporo virus genetic clusters I, II and III; SV/SV82 (SV/Sapporo virus 82); SV/Lond92 (SV/ London 92); and SV/PV (Parkville virus). RESULTS: SLVs were detected in association with 132 (9.2%) of all episodes; in 80 (5.6%) episodes SLV was the only gastroenteritis virus detected. The epidemic season of SLVs peaked from March to May concurrently with rotaviruses and astroviruses and overlapping withNorwalk-like viruses. Clinically SLV gastroenteritis was characterized by a mild diarrheal disease, being sharply different from the Norwalk-like virus-associated "winter vomiting disease." Rotavirus vaccination did not have any effect on the number of SLV episodes, but the intensity and duration of SLV-associated diarrhea were reduced in rotavirus-vaccinated children compared with placebo-vaccinated children (P = 0.0008). CONCLUSIONS: SLVs are common causative agents of acute gastroenteritis in young Finnish children. SLV disease is characterized by diarrhea, which is usually mild but can be severe. By an unknown mechanism rotavirus vaccine seems to reduce the severity of SLV-associated diarrhea.

Caliciviridae Infections↗

Human caliciviruses in acute gastroenteritis of young children in the community.

Episodes of acute gastroenteritis in prospectively followed children between 2 months and 2 years of age were examined for rotaviruses, enteric adenoviruses, astroviruses, and human caliciviruses, including both Norwalk-like viruses (NLVs) and Sapporo-like viruses (SLVs), using PCR and reverse transcription (RT)-PCR assays. A virus was identified in 60% (502/832) of all episodes and in 85% of the moderately severe or severe episodes. Human caliciviruses were as common as rotaviruses, both being detected in 29% of the cases. NLVs accounted for a 20% etiologic share of all cases; the clinical picture was a moderately severe disease with vomiting as a predominant symptom. SLVs were detected in 9% of the cases, the clinical picture being a mild diarrheal disease. Astroviruses were found in 10% and enteric adenoviruses in 6% of the cases. Diagnosis with PCR and RT-PCR methods increases the detection of all gastroenteritis viruses, particularly human caliciviruses. As a group, human caliciviruses are common causative agents of gastroenteritis in children <2 years of age in Finland, and, of these, NLVs cause more severe disease than SLVs.

Acute Disease↗

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 astrovirus-associated gastroenteritis in children under 2 years of age followed prospectively during a rotavirus vaccine trial.

This study evaluated the clinical significance of human astrovirus-associated gastroenteritis in young children in the community. Placebo- (n = 1207) and rhesus rotavirus tetravalent (RRV-TV) vaccine- (n = 1191) recipient children were followed from 2 mo to 2 y of age. Stool specimens from 1528 episodes of acute gastroenteritis (805 in the placebo group and 723 in the RRV-TV vaccine group) were tested for astrovirus with a sensitive reverse transcription-polymerase chain reaction (RT-PCR) assay and positive results were confirmed by Southern hybridization using probes specific for astrovirus serotypes 1 and 2. Astroviruses were detected in 144 (9%) episodes of gastroenteritis; 92% of the findings were serotype 1 and 6% were serotype 2. The astrovirus peak season was in winter. Of the 102 children who had gastroenteritis with astrovirus as the only diarrhoea virus in the stools, 72% had watery diarrhoea, 59% had vomiting, 26% had fever, 5% needed oral rehydration and 3% were hospitalized. Overall, the clinical severity of astrovirus gastroenteritis was much lower than that of rotavirus gastroenteritis. RRV-TV rotavirus vaccine did not protect against astrovirus gastroenteritis. It is concluded that astroviruses are common causative agents in acute gastroenteritis in young children, but the symptoms of astrovirus gastroenteritis are usually mild and the illness is therefore only of minor clinical significance.

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↗

Rotavirus vaccine studies in Europe.

Following the discovery and recognition of rotavirus as an important human enteropathogen, work towards the development of rotavirus vaccines was begun in the USA and Europe. The first candidate rotavirus vaccine was launched by SmithKline-RIT, Belgium, and studied in clinical trials in Finland, Yugoslavia, Italy, Switzerland, Austria and the UK. Efficacy trials in Finland of RIT 4237 strain live oral bovine rotavirus vaccine resulted in some fundamental findings about rotavirus immunity in humans: protection against disease rather than infection; better protection against severe than mild disease and heterotypic rather than homotypic protection. Another bovine rotavirus vaccine, strain WC-3, was studied briefly in France. Also studies of rhesus rotavirus vaccine were started early in Europe, and efficacy studies were carried out in Finland and Sweden. Recently, rhesus-human re-assortant tetravalent (RRV-TV) rotavirus vaccine was tested in a field trial in Finland this study was pivotal for the registration of the vaccine in the USA and European Union countries. Despite extensive experience with rotavirus vaccines in Europe, the need for such vaccines in many European countries still requires further assessment.

Animals↗

Rotavirus gastroenteritis in Finland: burden of disease and epidemiological features.

The burden of disease attributable to childhood rotavirus infection in Finland was assessed from data on hospital admissions for acute gastroenteritis and from reported virological diagnoses of rotavirus from 1985 to 1995. The mean number of hospitalizations (3584 annually in children under 5 y of age) corresponded to approximately 5.6% of the birth cohort. Rotavirus was estimated to be responsible for 54% of cases; accordingly, 3% of all children in Finland are hospitalized for rotavirus diarrhoea. The monthly distribution of hospitalizations for acute diarrhoea showed a similar pattern as monthly diagnoses of rotavirus, with a long epidemic period starting as early as November or December and lasting until June or even July. The prevalent rotavirus G-type throughout the study period was G1, which was detected in over 60% of the cases; however, in the season 1988-89 G4 was the prominent type. Improved case management has led to a shorter duration of hospital stay (3.3 d in 1985 vs. 2.3 d in 1995), but otherwise these was no significant trend for rotavirus gastroenteritis over the years. These findings underscore the need to control rotavirus gastroenteritis with a specific intervention, notably rotavirus vaccination.

Acute Disease↗

Serological evaluation of herpes simplex virus type 1 and type 2 infections in pregnancy.

OBJECTIVE: Serological evaluation of herpes simplex virus infections during pregnancy. METHODS: 2991 serum samples were obtained during 1st, 2nd, and 3rd trimester from 997 pregnant women. Baculovirus expressed glycoproteins gG1 (HSV-1) and gG2 (HSV-2) were used as antigens in ELISA for HSV-1 and HSV-2 IgG and IgA antibodies. RESULTS: The prevalence of HSV-1 gG1 antibodies was 70% and that of HSV-2 gG2 antibodies 16%. Among susceptible women we found five (0.6%) cases with serological evidence of primary HSV-2 infection during pregnancy. Evidence of active HSV-1 infection was found in nine (0.9%) cases. Decline of HSV-2 gG2 IgG antibody levels during pregnancy was pronounced compared with HSV-1 gG1 IgG antibody levels (p < 0.01); also the proportion of seroreversions was considerably higher among HSV-2 seropositives (25%) than among HSV-1 seropositives (3%) (p < 0.001). CONCLUSIONS: HSV-2 gG2 IgG antibodies were readily distinguished from HSV-1 gG1 IgG antibodies by the glycoprotein gG ELISAs. Serological assays for gG2 antibodies should guard against the decline of specific antibodies during pregnancy.

Adult↗

Rotavirus vaccines: development and use for the prevention of diarrhoeal disease.

Rotavirus causes annually 600 000 deaths of young children worldwide, mainly in developing countries. The burden of rotavirus disease is significant also in developed countries and has not diminished with improved hygiene. Natural protective immunity against severe rotavirus disease is built up during the first 2-3 years of life. Likewise, studies with live attenuated oral rotavirus vaccines have shown that the majority of severe episodes of rotavirus diarrhoea are preventable by oral immunization. Candidate rotavirus vaccines were first developed by tissue culture adaptation and attenuation of bovine and rhesus rotaviruses, both of which share the inner core VP6 group antigen with human group A rotaviruses. Subsequently, such heterologous rotaviruses were improved for use as human vaccines by reassortment with human rotaviruses; the resulting reassortants express human rotavirus VP7 surface antigens. A rhesus-human reassortant tetravalent (RRV-TV) rotavirus vaccine was licensed in the USA in 1998, and is recommended for universal immunization of healthy children; licensure in Europe is also imminent. In Finland, this vaccine has prevented 90% of severe episodes of rotavirus gastroenteritis. Protective efficacy of RRV-TV vaccine in developing countries is lower and a more intensive immunization schedule may be needed. Several other candidate rotavirus vaccines, including bovine-human reassortants, are being investigated.

Animals↗

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↗

Humoral and cell-mediated immune responses in humans to the NSP4 enterotoxin of rotavirus.

Rotavirus nonstructural protein NSP4 has recently been suggested to function as a viral enterotoxin and play a role in the pathophysiological mechanism whereby rotaviruses induce diarrhea. The ability of rotavirus NSP4 to stimulate a humoral immune response was examined in naturally infected children and adults, rotavirus vaccinated children, as well as a cellular immune response in adults. In this study, 10 of 10 naturally infected children and 9 of 10 rotavirus-vaccinated children showed a weak humoral IgG immune response to recombinant NSP4 (rNSP4) and/or a synthetic peptide corresponding to residues 114-134 of NSP4. Modest serum IgG antibody responses were detected in 20 of 20 adults. A cellular immune response to rNSP4 and/or NSP4(114-134) were detected in 8 of 10 adults measured either as a T-cell proliferative response (7 of 10), an increased production of IL-2 (6 of 10), or increased production of interferon-gamma (8 of 10). These results indicate that NSP4 induces a humoral immune response in humans and show for the first time that NSP4 stimulates a cellular immune response, possibly including cytolytic T-cells.

Adult↗

Community-based survey of paediatric diarrhoeal morbidity and home treatment practices in Finland.

To determine total diarrhoeal morbidity and current home case management practices, a recall study was conducted among 345 mothers whose 406 children under 5 y of age had had diarrhoea in the past 4 months. The seasonally adjusted annual diarrhoea incidence rate was 0.48 episodes/child/y. For home treatment, increased amounts of fluid were given in 93% and oral rehydration solution (ORS) in 37% of cases. However, when given, ORS was diluted with other fluids in 41% of cases. More than half (55%) of the children received increased or normal amounts of food during the diarrhoeal episode, but 7% of the children were kept fasting for at least 1 d. Use of antidiarrhoeal drugs was minimal (0.7%), but products containing lactic acid bacteria were given in 44% of cases. Case management practice in cases of diarrhoea at home have much improved during the last 20 y, but are still not optimal.

Child, Preschool↗

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↗