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Gothefors, Leif
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Publications (10 of 86) Show all publications
Carlsson, R. M., Gustafsson, L., Hallander, H. O., Ljungman, M., Olin, P., Gothefors, L., . . . Netterlid, E. (2015). Two consecutive randomized controlled pertussis booster trials in children initially vaccinated in infancy with an acellular vaccine: The first with a five-component Tdap vaccine to 5-year olds and the second with five- or monocomponent Tdap vaccines at age 14-15 years. Vaccine, 33(31), 3717-3725
Open this publication in new window or tab >>Two consecutive randomized controlled pertussis booster trials in children initially vaccinated in infancy with an acellular vaccine: The first with a five-component Tdap vaccine to 5-year olds and the second with five- or monocomponent Tdap vaccines at age 14-15 years
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2015 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 33, no 31, p. 3717-3725Article in journal (Refereed) Published
Abstract [en]

Prior study children from a DTaP efficacy trial were recruited at ages 5 and 15 years to randomized booster trials addressing immunogenicity and reactogenicity; 475 preschool children received mixed or separate injections of a reduced antigen vaccine (Tdap5, Sanofi Pasteur MSD) and an inactivated polio vaccine, and 230 adolescents received the same or another booster vaccine (Tdap1, SSI, Denmark). Pre-vaccination antibody concentrations against pertussis antigens were significantly higher at 15 than 5 years of age, probably due to natural boosting between the studies. Tdap5 induced comparable anti-PT concentrations at both ages, but antibody responses were significantly higher to filamentous haemagglutinin, pertactin and fimbriae 2/3 in adolescents. As expected, a higher amount of PT (Tdap1, 20 mu g) induced a stronger anti-PT response than a lower amount (Tdap5, 2.5 mu g). The frequency of adverse events was low and there were no serious adverse reactions. All local reactions had an early onset and a short duration. A large swelling or redness of more than half of the upper arm circumference was reported in 8/475 5-year-olds and in 6/230 15-year-olds. Children vaccinated with Tdap5 reported more moderate pain in adolescence than at preschool age, whereas itching was only reported in preschool children. Sweden introduced DTaP vaccines in 1996 after a 17-year hiatus with no general pertussis vaccination and pertussis was still endemic at the time of the studies. The frequency of adverse events was nevertheless low in both preschool children and adolescents and antibody responses were adequate. These studies document immunogenicity and reactogenicity in a trial cohort consecutively vaccinated with acellular pertussis vaccines from infancy to adolescence. (C) 2015 Elsevier Ltd. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Pertussis, Diphtheria, Tetanus, Vaccine, Acellular, Booster, Preschool, Adolescent, Immunization, munogenicity, Adverse effect, Reactogenicity
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-106778 (URN)10.1016/j.vaccine.2015.05.079 (DOI)000358096000018 ()26057135 (PubMedID)
Available from: 2015-08-14 Created: 2015-08-07 Last updated: 2018-06-07Bibliographically approved
Rinder, M., Tran, A. N., Bennet, R., Brytting, M., Cassel, T., Eriksson, M., . . . Johansen, K. (2014). Burden of severe rotavirus disease leading to hospitalization assessed in a prospective cohort study in Sweden. Scandinavian Journal of Infectious Diseases, 46(4), 294-302
Open this publication in new window or tab >>Burden of severe rotavirus disease leading to hospitalization assessed in a prospective cohort study in Sweden
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2014 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 46, no 4, p. 294-302Article in journal (Refereed) Published
Abstract [en]

Background: The aim of this prospective cohort study was to estimate the burden of severe disease caused by rotavirus-induced gastroenteritis in Swedish children aged <5 y. Methods: Rotavirus-positive children admitted to hospitals serving 3 geographical regions with 155,838 children aged <5 y, were offered inclusion in this 1-year study. Rotavirus strains identified were genotyped using multiplex PCR. Disease progression was documented through interviews and chart reviews. Results: In total, 604 children with rotavirus-induced gastroenteritis were included in the study. Forty-nine of 604 (8.1%) fulfilled the criteria for nosocomial infection. The minimum incidence was 388 per 100,000, with significant variability between study regions, ranging from 280 to 542 per 100,000. In all regions, the peak season occurred in February-April, but the season start varied, with first cases observed in October in the eastern region and December in the northern region. Genotypes identified differed between the regions: G1[P8] was most prevalent in all regions (77%), while the most varied pattern was observed in the western region, with G1[P8] observed in 61%, G4[P8] in 13%, G9[P8] in 10%, G2[P4] in 8%, and G3[P8] in 8% of the children. The median age of hospitalized children was 14 months and the median total duration of diarrhoea was 6.9 days. Sixty-eight percent reported a temperature >38.5 degrees C upon admission. Complications occurred in >10% of the children, with hypertonic dehydration (32/604) and seizures (10/604) occurring most frequently. Conclusions: Rotaviruses may cause severe febrile acute gastroenteritis leading to dehydration requiring acute rehydration in hospital. In addition, further complications occurred in >10% of hospitalized children.

Keywords
Rotavirus, incidence, hospitalization, complication, genotype
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-88324 (URN)10.3109/00365548.2013.876511 (DOI)000333045600008 ()
Available from: 2014-06-16 Created: 2014-04-30 Last updated: 2018-06-07Bibliographically approved
Prymula, R., Bergsaker, M. R., Esposito, S., Gothefors, L., Man, S., Snegova, N., . . . Willems, P. (2014). Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine versus one dose of monovalent varicella vaccine: a multicentre, observer-blind, randomised, controlled trial. The Lancet, 383(9925), 1313-1324
Open this publication in new window or tab >>Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine versus one dose of monovalent varicella vaccine: a multicentre, observer-blind, randomised, controlled trial
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2014 (English)In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 383, no 9925, p. 1313-1324Article in journal (Refereed) Published
Abstract [en]

Background Rates of varicella have decreased substantially in countries implementing routine varicella vaccination. Immunisation is possible with monovalent varicella vaccine or a combined measles-mumps-rubella-varicella vaccine (MMRV). We assessed protection against varicella in naive children administered one dose of varicella vaccine or two doses of MMRV. Methods This study was done in ten European countries with endemic varicella. Healthy children aged 12-22 months were randomised (3: 3: 1 ratio, by computer-generated randomisation list, with block size seven) to receive 42 days apart (1) two doses of MMRV (MMRV group), or (2) MMR at dose one and monovalent varicella vaccine at dose two (MMR+V group), or (3) two doses of MMR (MMR group; control). Participants and their parents or guardians, individuals involved in assessment of any outcome, and sponsor staff involved in review or analysis of data were masked to treatment assignment. The primary efficacy endpoint was occurrence of confirmed varicella (by detection of varicella zoster virus DNA or epidemiological link) from 42 days after the second vaccine dose to the end of the first phase of the trial. Cases were graded for severity. Efficacy analyses were per protocol. Safety analyses included all participants who received at least one vaccine dose. This trial is registered with ClinicalTrials.gov, number NCT00226499. Findings Between Sept 1, 2005, and May 10, 2006, 5803 children (mean age 14.2 months, SD 2.5) were vaccinated. In the efficacy cohort of 5285 children, the mean duration of follow-up in the MMRV group was 36 months (SD 8.8), in the MMR+V group was 36 months (8.5) and in the MMR group was 35 months (8.9). Varicella cases were confirmed for 37 participants in the MMRV group (two moderate to severe), 243 in the MMR+V group, and 201 in the MMR group. Second cases occurred for three participants (all in the MMR+V group). Varicella cases were moderate to severe for two participants in the MMRV group, 37 in the MMR+V group (one being a second case that followed a mild first case); and 117 in the MMR group. Efficacy of two-dose MMRV against all varicella was 94.9% (97.5% CI 92.4-96.6), and against moderate to severe varicella was 99.5% (97.5-99.9). Efficacy of one-dose varicella vaccine against all varicella was 65.4% (57.2-72.1), and against moderate to severe varicella (post hoc) was 90.7% (85.9-93.9). The most common adverse event in all groups was injection-site redness (up to 25% of participants). Within 15 days after dose one, 57.4% (95% CI 53.9-60.9) of participants in the MMRV group reported fever of 38 degrees C or more, by contrast with 44.5% (41.0-48.1) with MMR+V, and 39.8% (33.8-46.1) with MMR. Eight serious adverse events were deemed related to vaccination (three MMRV, four MMR+V, one MMR). All resolved within the study period. Interpretation These results support the implementation of two-dose varicella vaccination on a short course, to ensure optimum protection from all forms of varicella disease.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-88383 (URN)10.1016/S0140-6736(12)61461-5 (DOI)000334104900030 ()
Available from: 2014-05-27 Created: 2014-05-05 Last updated: 2018-06-07Bibliographically approved
Myléus, A., Hernell, O., Gothefors, L., Hammarström, M.-L., Persson, L.-Å., Stenlund, H. & Ivarsson, A. (2012). Early infections are associated with increased risk for celiac disease: an incident case-referent study. BMC Pediatrics, 12(1), 194
Open this publication in new window or tab >>Early infections are associated with increased risk for celiac disease: an incident case-referent study
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2012 (English)In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 12, no 1, p. 194-Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Celiac disease is defined as a 'chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals'. Sweden has experienced an "epidemic" of celiac disease in children below two years of age. Celiac disease etiology is considered multifactorial; however, little is known regarding potential risk- or protecting factors. We present data on the possible association between early infectious episodes and celiac disease, including their possible contribution to the Swedish celiac disease epidemic.

METHODS: A population-based incident case-referent study (475 cases, 950 referents) with exposure information obtained via a questionnaire (including family characteristics, infant feeding, and the child's general health) was performed. Celiac disease cases were diagnosed before two years of age, fulfilling the diagnostic criteria of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. Referents were randomly selected from the national population register after fulfilling matching criteria. The final analyses included 954 children, 373 (79%) cases and 581 (61%) referents, with complete information on main variables of interest in a matched set of one case with one or two referents.

RESULTS: Having three or more parental-reported infectious episodes, regardless of type of infection, during the first six months of life was associated with a significantly increased risk for later celiac disease, and this remained after adjusting for infant feeding and socioeconomic status (odds ratio [OR] 1.5; 95% confidence interval [CI], 1.1-2.0; P=0.014). The celiac disease risk increased synergistically if, in addition to having several infectious episodes, infants were introduced to dietary gluten in large amounts, compared to small or medium amounts, after breastfeeding was discontinued (OR 5.6; 95% CI, 3.1-10; P<0.001).

CONCLUSION: This study suggests that having repeated infectious episodes early in life increases the risk for later celiac disease. In addition, we found a synergistic effect between early infections and daily amount of gluten intake, more pronounced among infants for whom breastfeeding had been discontinued prior to gluten introduction. Regarding contribution to the Swedish celiac disease epidemic, which partly was attributed to concurrent changes in infant feeding, early infections probably made a minor contribution via the synergistic effect with gluten amount.

National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-64524 (URN)10.1186/1471-2431-12-194 (DOI)23249321 (PubMedID)
Available from: 2013-03-08 Created: 2013-01-31 Last updated: 2018-06-08Bibliographically approved
Myleus, A., Stenlund, H., Hernell, O., Gothefors, L., Hammarström, M.-L., Persson, L.-å. & Ivarsson, A. (2012). Early vaccinations are not risk factors for Celiac Disease. Pediatrics, 130(1), E63-E70
Open this publication in new window or tab >>Early vaccinations are not risk factors for Celiac Disease
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2012 (English)In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 130, no 1, p. E63-E70Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To investigate if changes in the national Swedish vaccination program coincided with changes in the celiac disease (CD) incidence rate in infants (ie, the Swedish CD Epidemic), and to assess the potential association between these vaccinations and CD risk.

METHODS: All studies were based on the National Swedish Childhood Celiac Disease Register. Using an ecological approach, we plotted changes over time in the national vaccination program in the graph displaying CD incidence rate. A population-based incident case-referent study of invited infants was performed. Exposure information was received through a questionnaire and child health clinic records. Vaccines explored were diphtheria/tetanus, pertussis (acellular), polio (inactivated), Haemophilus influenzae type b (conjugated), measles/mumps/rubella, and live attenuated bacillus Calmette-Guerin (BCG) in children with increased tuberculosis risk. Findings were subjected to a birth cohort analysis.

RESULTS: Introduction of pertussis vaccine coincided in time with decreasing CD incidence rates. In the infant case-referent study, however, neither vaccination against pertussis (odds ratio 0.91; 95% confidence interval 0.60-1.4), nor against Haemophilus influenzae type b or measles/mumps/rubella was associated with CD. Coverage for the diphtheria/tetanus and polio vaccines was 99%. BCG was associated with reduced risk for CD (adjusted odds ratio 0.54; 95% confidence interval 0.31-0.94). Discontinuation of general BCG vaccination did not affect the cumulative incidence of CD at age 15 years.

CONCLUSIONS: Early vaccinations within the national Swedish program were not associated with CD risk, nor could changes in the program explain the Swedish epidemic. A protective effect by BCG was suggested, which could be subject to further studies. Pediatrics 2012;130:e63-e70

Keywords
celiac disease, infant, epidemiology, vaccines
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-57651 (URN)10.1542/peds.2011-2806 (DOI)000305905900009 ()
Available from: 2012-08-09 Created: 2012-08-08 Last updated: 2018-06-08Bibliographically approved
Gothefors, L. & Trollfors, B. (2012). Vaccinationsprogrammet efter HPV? Vad övrigt är, är tystnad. [Letter to the editor]. Läkartidningen, 109(8), 384-384
Open this publication in new window or tab >>Vaccinationsprogrammet efter HPV? Vad övrigt är, är tystnad.
2012 (Swedish)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 8, p. 384-384Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Läkartidningen förlag AB, 2012
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-101470 (URN)22509661 (PubMedID)
Available from: 2015-03-31 Created: 2015-03-31 Last updated: 2018-06-07Bibliographically approved
Gothefors, L. & Hernell, O. (2011). Diarré och magsjuka – prevention och behandling. Små & stora nyheter (Maj)
Open this publication in new window or tab >>Diarré och magsjuka – prevention och behandling
2011 (Swedish)In: Små & stora nyheter, ISSN ISSN 1400-4186, no MajArticle in journal (Other (popular science, discussion, etc.)) Published
Place, publisher, year, edition, pages
Stockholm: Semper, 2011
Identifiers
urn:nbn:se:umu:diva-45246 (URN)
Available from: 2011-06-29 Created: 2011-06-29 Last updated: 2018-06-08Bibliographically approved
Carlsson, R.-M., Blennow, M. & Gothefors, L. (2011). Vaccination av barn och ungdomar (ingår i Läkemedelsboken 2011-2012). In: Odeberg H et al (red) (Ed.), Läkemedelsboken 2011-2012 (pp. 177-191). Uppsala: Läkemedelsverket
Open this publication in new window or tab >>Vaccination av barn och ungdomar (ingår i Läkemedelsboken 2011-2012)
2011 (Swedish)In: Läkemedelsboken 2011-2012 / [ed] Odeberg H et al (red), Uppsala: Läkemedelsverket , 2011, p. 177-191Chapter in book (Refereed)
Place, publisher, year, edition, pages
Uppsala: Läkemedelsverket, 2011
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:umu:diva-52211 (URN)9789197960502 (ISBN)
Available from: 2012-02-13 Created: 2012-02-13 Last updated: 2018-06-08Bibliographically approved
Van der Wielen, M., Giaquinto, C., Gothefors, L., Huelsse, C., Huet, F., Littmann, M., . . . Van Damme, P. (2010). Impact of community-acquired paediatric rotavirus gastroenteritis on family life: data from the REVEAL study.. BMC Family Practice, 11, 22
Open this publication in new window or tab >>Impact of community-acquired paediatric rotavirus gastroenteritis on family life: data from the REVEAL study.
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2010 (English)In: BMC Family Practice, ISSN 1471-2296, E-ISSN 1471-2296, Vol. 11, p. 22-Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Rotavirus is the leading cause of acute gastroenteritis (AGE) and the most frequent cause of severe diarrhoea in children aged less than 5 years. Although the epidemiology of rotavirus gastroenteritis (RVGE) is well documented, there are few data on the impact of RVGE on the families of affected children. METHODS: Data associated with the burden of RVGE, including number of working days lost, levels of parental stress, the need for alternative childcare arrangements and additional nappies used, were extracted from questionnaires completed by parents of children participating in a prospective, multicentre, observational study (Rotavirus gastroenteritis Epidemiology and Viral types in Europe Accounting for Losses in public health and society, REVEAL), conducted during 2004-2005 in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom to estimate the incidence of RVGE in children aged less than 5 years seeking medical care as a result of AGE. RESULTS: 1102 children with RVGE were included in the present analysis. The proportion of RVGE cases that required at least one parent or other person to be absent from work was 39%-91% in the hospital setting, 44%-64% in the emergency department, and 20%-64% in primary care. Self-reported levels of parental stress were generally high (mean stress levels, > or = 5 on a 10-point visual analogue scale). Additional childcare arrangements were required in up to 21% of RVGE episodes. The mean number of nappies used per day during RVGE episodes was approximately double that used when the child was not ill. CONCLUSIONS: Paediatric RVGE cases cause disruption to families and parental stress. The burden of RVGE on children and their families could be substantially reduced by routine rotavirus vaccination of infants.

Keywords
Rotavirus, gastroenteritis, family life
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-35026 (URN)10.1186/1471-2296-11-22 (DOI)000275834000001 ()20230601 (PubMedID)
Available from: 2010-07-02 Created: 2010-07-02 Last updated: 2018-06-08Bibliographically approved
Itzler, R., Koch, G., Matson, D. O., Gothefors, L., Van Damme, P., Dinubile, M. J. & Heaton, P. M. (2010). Robustness of the healthcare utilization results from the Rotavirus Efficacy and Safety Trial (REST) evaluating the human-bovine (WC3) reassortant pentavalent rotavirus vaccine (RV5).. BMC Pediatrics, 10(1), 42
Open this publication in new window or tab >>Robustness of the healthcare utilization results from the Rotavirus Efficacy and Safety Trial (REST) evaluating the human-bovine (WC3) reassortant pentavalent rotavirus vaccine (RV5).
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2010 (English)In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 10, no 1, p. 42-Article in journal (Refereed) Published
Abstract [en]

ABSTRACT: BACKGROUND: The Rotavirus Efficacy and Safety Trial was a placebo-controlled Phase III study that evaluated the safety and efficacy of a three-dose pentavalent rotavirus vaccine (RV5) including its effect on healthcare utilization for rotavirus gastroenteritis (RVGE). The per-protocol (PP) analyses, which counted events occurring 14 days after dose 3 among infants without protocol violations, have already been published. This paper evaluates the consistency of the healthcare utilization results based on the modified intention to treat (MITT) analyses with the PP analyses. The MITT analyses include all infants receiving at least one dose of vaccine or placebo and follow-up begins after dose 1. The paper also explores the consistency of the results for different subgroups of the study population with different types of surveillance. METHODS: Data on healthcare utilization for acute gastroenteritis were collected via telephone interviews after administration of the first dose. Parents were either contacted every 6 weeks or every 2 weeks depending on the substudy in which they were enrolled. Those contacted every 2 weeks were also asked to complete symptom diaries. Poisson regression was used to evaluate the effect of RV5 on the rates of RVGE-associated healthcare encounters in all of the analyses. RESULTS: In the first 2 years after vaccination, RV5 reduced the combined rate of hospitalizations and emergency department (ED) visits 88.9% (95% CI: 84.9, 91.9) for all RVGE regardless of serotype in the MITT analysis compared with a 94.5% (95% CI: 91.2, 96.6) reduction based on the G1-G4 PP analysis. By type of surveillance, the rate reductions for the G1-G4 PP analysis were 91.0 % (95% CI: 81.7, 95.5) and 95.9% (95% CI: 92.2, 97.8) among parents contacted every 2 weeks (number evaluable =4,451) and every 6 weeks (number evaluable =52,683) respectively. CONCLUSIONS: Our analyses demonstrated that the effect of RV5 on reducing the rate of hospitalizations and ED visits based on the MITT analyses were generally consistent with the PP analyses. The rate of events for subgroups with different intensities of surveillance differed but the effect of RV5 on the relative rate reductions were consistent with the results that have already been published. Trial Registration ClinicalTrials.gov number, NCT00090233.

Keywords
Rotavirus, vaccine
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
urn:nbn:se:umu:diva-35082 (URN)10.1186/1471-2431-10-42 (DOI)000279953400002 ()20540778 (PubMedID)
Available from: 2010-07-06 Created: 2010-07-06 Last updated: 2018-06-08Bibliographically approved
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