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  • 1.
    Ahlm, Clas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Settergren, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Gothefors, Leif
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Juto, Per
    Nephropathia epidemica (hemorrhagic fever with renal syndrome) in children: clinical characteristics.1994Ingår i: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 13, nr 1, s. 45-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The clinical characteristics of serologically verified nephropathia epidemica, the Scandinavian form of hemorrhagic fever with renal syndrome, were studied in Swedish children who were < 15 years of age. In 1990 to 1992, 14 cases were prospectively followed. A retrospective survey during 1984 to 1990 disclosed another 18 cases. Among the 32 cases (20 boys, 12 girls, 3 to 15 years of age; median age, 11 years), the most common symptoms were fever (100%), headache (100%), abdominal pain (93%), vomiting (91%) and back pain (76%). Laboratory findings included elevated serum creatinine concentration (19 of 28) and thrombocytopenia (7 of 22). Urinalysis showed proteinuria (31 of 31 patients) and hematuria (24 of 30). Six children had mild hemorrhagic manifestations (epistaxis, metrorrhagia, and petechiae). No severe complications occurred. The clinical symptoms of children with nephropathia epidemica seem to be similar to those found among adult nephropathia epidemica cases.

  • 2. Cohen, Cheryl
    et al.
    Walaza, Sibongile
    Moyes, Jocelyn
    Groome, Michelle
    Tempia, Stefano
    Pretorius, Marthi
    Hellferscee, Orienka
    Dawood, Halima
    Chhagan, Meera
    Naby, Fathima
    Haffejee, Summaya
    Variava, Ebrahim
    Kahn, Kathleen
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Nzenze, Susan
    Tshangela, Akhona
    von Gottberg, Anne
    Wolter, Nicole
    Cohen, Adam L.
    Kgokong, Babatyi
    Venter, Marietjie
    Madhi, Shabir A.
    Epidemiology of Viral-associated Acute Lower Respiratory Tract Infection Among Children < 5 Years of Age in a High HIV Prevalence Setting, South Africa, 2009-20122015Ingår i: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 34, nr 1, s. 66-72Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Data on the epidemiology of viral-associated acute lower respiratory tract infection (LRTI) from high HIV prevalence settings are limited. We aimed to describe LRTI hospitalizations among South African children aged < 5 years. Methods: We prospectively enrolled hospitalized children with physician-diagnosed LRTI from 5 sites in 4 provinces from 2009 to 2012. Using polymerase chain reaction (PCR), nasopharyngeal aspirates were tested for 10 viruses and blood for pneumococcal DNA. Incidence was estimated at 1 site with available population denominators. Results: We enrolled 8723 children aged < 5 years with LRTI, including 64% < 12 months. The case-fatality ratio was 2% (150/8512). HIV prevalence among tested children was 12% (705/5964). The overall prevalence of respiratory viruses identified was 78% (6517/8393), including 37% rhinovirus, 26% respiratory syncytial virus (RSV), 7% influenza and 5% human metapneumovirus. Four percent (253/6612) tested positive for pneumococcus. The annual incidence of LRTI hospitalization ranged from 2530 to 3173/100,000 population and was highest in infants (8446-10532/100,000). LRTI incidence was 1.1 to 3.0-fold greater in HIV-infected than HIV-uninfected children. In multivariable analysis, compared to HIV-uninfected children, HIV-infected children were more likely to require supplemental-oxygen [odds ratio (OR): 1.3, 95% confidence interval (CI): 1.1-1.7)], be hospitalized > 7 days (OR: 3.8, 95% CI: 2.8-5.0) and had a higher case-fatality ratio (OR: 4.2, 95% CI: 2.6-6.8). In multivariable analysis, HIV-infection (OR: 3.7, 95% CI: 2.2-6.1), pneumococcal coinfection (OR: 2.4, 95% CI: 1.1-5.6), mechanical ventilation (OR: 6.9, 95% CI: 2.7-17.6) and receipt of supplemental-oxygen (OR: 27.3, 95% CI: 13.2-55.9) were associated with death. Conclusions: HIV-infection was associated with an increased risk of LRTI hospitalization and death. A viral pathogen, commonly RSV, was identified in a high proportion of LRTI cases.

  • 3. Johansson, A
    et al.
    Berglund, L
    Gothefors, Leif
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Sjöstedt, A
    Tärnvik, A
    Ciprofloxacin for treatment of tularemia in children.2000Ingår i: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 19, nr 5, s. 449-53Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In our sample of 12 patients ciprofloxacin was satisfactory for outpatient treatment of tularemia in children.

  • 4.
    Lundberg, Thorbjörn
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Hellström, Sten
    Sandström, Herbert
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Development and Validation of a New Grading Scale for Otitis Media2013Ingår i: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 32, nr 4, s. 341-345Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Grading of acute otitis media (AOM) is important in clinical situations as well as in research. Current grading scales for AOM have used a 6 to 9 point scoring system primarily based on variation of redness and bulging of the tympanic membrane (TM). This study aimed to develop and validate a new scale for grading AOM. Method: The scale was developed in 3 stages based on 32 patients with images taken of the TM when a child attended healthcare centre with othalgia and at follow-up visits. Content validity was used as the method for the first 2 stages. An expert panel reviewed the scale and repeated the process on a revised scale. Reliability was tested with a different expert panel that used the final scale on a sample of TM images in a test-retest and inter-rater and intra-rater agreements were calculated. Results: The scale was developed in 3 steps using expert committees. During the process the description of vascularization was judged to be of insufficient importance for our scale. Inter-rater agreement was moderate (kappa = 0.52) and intra-rater agreement was good (kappa = 0.66 to 0.89) in the test-retest of the final scale. Conclusions: The developed AOM image-based grading scale demonstrates substantial inter- and intra-rater reliability with potential use in clinical research and telemedicine applications. Furthermore, the parameter "redness of TM" is of less importance in our scale as compared with other available grading systems.

  • 5. Msimang, Veerle M. Y.
    et al.
    Page, Nicola
    Groome, Michelle J.
    Moyes, Jocelyn
    Cortese, Margaret M.
    Seheri, Mapaseka
    Kahn, Kathleen
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Chagan, Meera
    Madhi, Shabir A.
    Cohen, Cheryl
    Impact of Rotavirus Vaccine on Childhood Diarrheal Hospitalization After Introduction Into the South African Public Immunization Program2013Ingår i: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 32, nr 12, s. 1359-1364Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Oral rotavirus vaccine was introduced into the South African routine immunization program in August 2009 administered at 6 and 14 weeks with no catch-up. We described the change in rotavirus-associated diarrheal hospitalizations among children <5 years at 3 sentinel sites from 2009 through 2011. Methods: During 2009 through 2011, we compared the proportion of enrolled children aged <5 years hospitalized with acute gastroenteritis and testing rotavirus positive. We used hospital data to determine the change in diarrhea hospitalizations and estimated total numbers of rotavirus hospitalizations by adjusting for nonenrolled patients. Stool samples were tested for rotavirus using enzyme immunoassay. Results: In 2009 (May-December), 46% (404/883) of samples among children <5 years tested rotavirus positive, decreasing to 33% (192/580) (P < 0.001) in 2010 and 29% (113/396) (P < 0.001) in 2011. Compared with May-December 2009, total diarrhea hospitalizations among children aged <5 years was one-third lower in May-December of 2010 and 2011. Among infants, adjusted rotavirus hospitalizations were 61% (n = 267) and 69% (n = 214) lower, respectively, in 2010 and 2011 when compared with 2009 (n = 689), and 45 and 50 percentage points greater than the reduction in rotavirus-negative cases. Among children <5 years, rotavirus hospitalizations were 54% and 58% lower in 2010 and 2011, compared with 2009 (40 and 44 percentage points greater than reduction in rotavirus-negative cases). Rotavirus reductions occurred in rural and urban settings. Conclusion: Using published estimates of rotavirus hospitalization burden, we estimate that at least 13,000 to 20,000 hospitalizations in children <2 years were prevented in the 2 years after rotavirus vaccine introduction.

  • 6. Nzenze, Susan A
    et al.
    Shiri, Tinevimbo
    Nunes, Marta C
    Klugman, Keith P
    Kahn, Kathleen
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Twine, Rhian
    de Gouveia, Linda
    von Gottberg, Anne
    Madhi, Shabir A
    Temporal changes in pneumococcal colonization in a rural African community with high HIV prevalence following routine infant pneumococcal immunization2013Ingår i: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 32, nr 11, s. 1270-1278Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Pneumococcal conjugate vaccine (PCV) immunization of children decreases their risk of nasopharyngeal acquisition of vaccine serotypes. We studied the impact of routine infant PCV immunization alone on the epidemiology of nasopharyngeal pneumococcal colonization among a rural African community with high prevalence of HIV positivity.

    Methods: Two cross-sectional surveys were undertaken in a rural South African community from May to October 2009 (period 1) and 2011 (period 2). Seven-valent PCV was introduced into the public immunization program for infants in April 2009, without catch-up campaign for older children. Randomly selected households with at least 1 child <2 years of age were recruited. Nasopharyngeal swabs from all consenting household members were obtained for Streptococcus pneumoniae culture and serotyping by Quellung method.

    Results: The median ages (SD) of children enrolled were 4.32 (SD, 3.4) and 3.80 (SD, 3.4) years in periods 1 and 2, respectively. Overall, the prevalence of vaccine serotype colonization declined from 18.3% (368/2010) in period 1 to 11.4% (418/3659) by period 2 (P < 0.0001). This included reductions (adjusted risk ratio) of 50% [95% confidence interval (95% CI): 0.42-0.59], 34% (95% CI: 0.48-0.92) and 64% (95% CI: 0.18-0.74) in age groups < 2 years, 6-12 years and adults. The prevalence of vaccine serotype colonization among primary caregivers decreased from 10.2% to 5.4% (P <= 0.001) by period 2. The prevalence of nonvaccine serotype colonization increased by 35% (95% CI: 1.17-1.56) among <2-year-old children by period 2, while it declined by 45-54% among adolescents and adults.

    Conclusions: An indirect effect of PCV7 was realized in a high HIV prevalence setting within 2 years of PCV introduction. The unexpected decline in nonvaccine serotypes colonization among adolescents/adults may indicate lag in replacement colonization by nonvaccine serotypes in this group.

  • 7.
    Silfverdal, Sven Arne
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hogh, Birthe
    Department of Pediatrics, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
    Bergsaker, Marianne Riise
    Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway.
    Skerlikova, Helena
    GPP Practice, Dolny Kubin, Slovakia.
    Lommel, Patricia
    Global Clinical Development Center, GlaxoSmithKline Biologicals, Rixensart, Belgium.
    Borys, Dorota
    Global Clinical Development Center, GlaxoSmithKline Biologicals, Rixensart, Belgium.
    Schuerman, Lode
    Global Clinical Development Center, GlaxoSmithKline Biologicals, Rixensart, Belgium.
    Immunogenicity of a 2-dose priming and booster vaccination with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine2009Ingår i: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 28, nr 10, s. e276-282Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was determined following a simplified 2-dose priming and the more commonly employed 3-dose priming both followed by a booster dose. METHODS: A total of 351 healthy subjects were primed with PHiD-CV at either 3 and 5 or 3, 4 and 5 months of age followed in all subjects by a booster dose at 11 to 12 months of age. Serotype-specific pneumococcal responses were measured by 22F-inhibition ELISA and opsonophagocytic assays 1 month following primary and booster vaccinations. RESULTS: Depending on the serotype, the percentages of subjects reaching the ELISA antibody threshold of 0.2 microg/mL were 92.8% to 98.0% following 2 primary doses and 96.1% to 100% following 3 primary doses except for serotype 6B (55.7% and 63.1%, respectively) and serotype 23F (69.3% and 77.6%, respectively). Opsonophagocytic activity (OPA) could be measured in 74.4% to 100% and 88.9% to 100% of the subjects after the 2-dose or 3-dose priming, respectively, except for serotype 1 (60.8% and 62.9%, respectively). In both groups, robust increases in ELISA antibodies and OPA titers were observed for all serotypes after the booster dose. Higher postprimary and postbooster ELISA antibody levels and OPA titers were observed for most serotypes following the 3+1 schedule. CONCLUSION: PHiD-CV was immunogenic in both schedules, but further effectiveness data are needed to fully understand the public health benefit to be expected from these schedules in terms of prevention against invasive and mucosal infections.

  • 8.
    Silfverdal, Sven Arne
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Skerlikova, Helena
    Zanova, Maria
    Papúchová, Danica
    Traskine, Magali
    Borys, Dorota
    Schuerman, Lode
    Anamnestic Immune Response in 3- to 4-year-old Children Previously Immunized With 10-valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine as 2 Dose or 3 Dose Priming and a Booster Dose in the First Year of Life.2011Ingår i: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 30, nr 9, s. e155-e163Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:: Immunogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae proteind conjugate vaccine (PHiD-CV), administered as 2 dose or 3 dose priming followed by a booster dose, has been described previously. The present study evaluated immunologic memory following PHiD-CV vaccination according to these vaccination schedules. METHODS:: A dose of PHiD-CV (to test anamnestic responses) was administered to 172 children at 36 to 46 months of age; 110 of them had previously been vaccinated with PHiD-CV according to 2 + 1 or 3 + 1 schedules (PHiD-CV [2 + 1] and PHiD-CV [3 + 1] groups) and 62 were unprimed age-matched controls. To measure immune responses before and 7 to 10 days after the PHiD-CV dose, 22F-inhibition enzyme-linked immunosorbent assay and opsonophagocytic activity (OPA) assay were used. RESULTS:: Serotype-specific IgG geometric mean concentrations (GMCs) and OPA geometric mean titers (GMTs) increased substantially (from before to 7 to 10 days after the additional PHiD-CV dose) for all 10 vaccines and 2 cross-reactive serotypes (6A and 19A) in the children previously vaccinated with PHiD-CV, regardless of the vaccination schedule used. Antibody GMCs and OPA GMTs after the administration of the PHiD-CV dose were markedly higher in both previously PHiD-CV-vaccinated groups than in the unprimed control group, clearly demonstrating prior induction of immunologic memory. Antiprotein D antibody GMCs had also increased substantially from before to 7 to 10 days after vaccination in all 3 groups, with higher antibody GMCs in the previously vaccinated groups than in the control group. CONCLUSION:: PHiD-CV vaccination according to 2 + 1 or 3 + 1 schedules resulted in comparable anamnestic immune responses. These findings suggest that similar protective efficacy may be achieved with both the schedules.

  • 9. Silfverdal, Sven-Arne
    et al.
    Bodin, Lennart
    Ulanova, Marina
    Hahn-Zoric, Mirjana
    Hanson, Lars A
    Olcen, Per
    Long term enhancement of the IgG2 antibody response to Haemophilus influenzae type b by breast-feeding.2002Ingår i: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 21, nr 9, s. 816-21Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    SUBJECTS: Sets of sera were obtained from 30 children <6 years of age with invasive type b (Hib) infection and their mothers. Duration and mode of breast-feeding were monitored. Titers of IgG1, IgG2, IgA and IgM antibodies against Hib capsular polysaccharide were determined in sera taken during the acute illness and during early and late convalescence. RESULTS: Children 18 months or older with longer durations of exclusive breast-feeding (13 weeks or more; mean, 19.3 weeks) had higher Hib antibody concentrations of the IgG1, IgG2, IgA and IgM isotypes than those with a shorter duration of exclusive breast-feeding (<13 weeks; mean, 5.4 weeks). The difference was greatest for the IgG2 isotype. In regression analyses the association between the duration of exclusive breast-feeding and the anti-Hib IgG2 concentration was significant when breast-feeding, type of Hib infection, maternal Hib antibody titer and age were used as explanatory factors. In the group of 14 children <18 months of age no significant differences were noted. DISCUSSION: This study indicates the presence of a long lasting enhancing effect of breast-feeding on the antibody response to Hib in children, in particular on IgG2 Hib antibody production. This may result from the content in the milk of IFN-gamma and IFN-gamma-producing cells and possibly other factors, which can support IgG2 antibody production.

  • 10. Vesikari, Timo
    et al.
    Richardus, Jan Hendrik
    Berglund, Johan
    Korhonen, Tiina
    Flodmark, Carl-Erik
    Lindstrand, Ann
    Silfverdal, Sven Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Bambure, Vinod
    Caplanusi, Adrian
    Dieussaert, Ilse
    Roy-Ghanta, Sumita
    Vaughn, David W.
    Immunogenicity and Safety of a Trivalent Inactivated Influenza Vaccine in Children 6 Months to 17 Years of Age, Previously Vaccinated with an AS03-Adjuvanted A(H1N1)Pdm09 Vaccine Two Open-label, Randomized Trials2015Ingår i: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 34, nr 7, s. 774-782Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: During the influenza pandemic 2009-2010, an AS03-adjuvanted A(H1N1) pdm09 vaccine was used extensively in children 6 months of age and older, and during the 2010-2011 influenza season, the A(H1N1) pdm09 strain was included in the seasonal trivalent inactivated influenza vaccine (TIV) without adjuvant. We evaluated the immunogenicity and safety of TIV in children previously vaccinated with the AS03-adjuvanted A(H1N1) pdm09 vaccine. Methods: Healthy children were randomized (1:1) to receive TIV or a control vaccine. Children were aged 6 months to 9 years (n = 154) and adolescents 10-17 years (n = 77) when they received AS03-adjuvanted A(H1N1) pdm09 vaccine at least 6 months before study enrolment. Hemagglutination inhibition (HI) and neutralizing antibody responses against the A(H1N1) pdm09 strain were evaluated before (day 0) and at day 28 and month 6 after study vaccination. Reactogenicity was assessed during the 7 day postvaccination period, and safety was assessed for 6 months. Results: At day 0, >93.9% of all children had HI titers >= 1:40 for the A(H1N1) pdm09 strain, which increased to 100% at both day 28 and month 6 in the TIV group. Between days 0 and 28, HI antibody geometric mean titers against A(H1N1) pdm09 increased by 9-fold and 4-fold in children 6 months to 9 years of age and 10-17 years of age, respectively. Conclusion: AS03-adjuvanted A(H1N1) pdm09 vaccine-induced robust immune responses in children that persisted into the next season, yet were still boosted by TIV containing A(H1N1) pdm09. The reactogenicity and safety profile of TIV did not appear compromised by prior receipt of AS03adjuvanted A(H1N1) pdm09 vaccine.

  • 11. Vesikari, Timo
    et al.
    Silfverdal, Sven-Arne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Jordanov, Emilia
    Feroldi, Emmanuel
    A Randomized, Controlled Study of DTaP-IPV-HB-PRP-T, a Fully Liquid Hexavalent Vaccine, Administered in a 3-,5-and 11-to 12-month Schedule2017Ingår i: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 36, nr 1, s. 87-93Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: To assess the immunogenicity and safety of a fully liquid, ready-to-use hexavalent DTaP-IPV-HB-PRP-T vaccine when administered in a 2 + 1 schedule at 3, 5 and 11-12 months of age.

    Methods: Phase III, randomized, active-controlled, observer-blind, multi-center study. Infants were randomized to receive DTaP-IPV-HB-PRP-T (N = 275) or a licensed control hexavalent vaccine (DTaP-IPV-HB//PRPNT: N = 275), both given in coadministration with Prevenar 13. Serum was analyzed for immune responses to all vaccine antigens. Noninferiority of DTaP-IPV-HB-PRP-T to the control vaccine was tested at completion of the primary series using predefined seroprotection (SP) rate and vaccine response (VR) rates. Safety was assessed using parental reports.

    Results: Noninferiority of DTaP-IPV-HB-PRP-T to the control vaccine was demonstrated postdose 3 for each antigen, and the SP (for D, T, poliovirus 1, 2 and 3, hepatitis B and polyribosylribitol phosphate) and VR rates (for pertussis toxin and filamentous hemagglutinin) were high in each group. SP rates for D, T, polio 1, 2, 3 and VR rates for pertussis toxin and filamentous hemagglutinin were similar in each group. For hepatitis B, SP rate was slightly higher for DTaP-IPV-HB//PRP similar to T (99.6%) than DTaP-IPV-HB-PRP-T (96.4%), and for PRP, SP rate was higher for DTaP-IPV-HB-PRP-T (93.5%) than DTaP-IPV-HB//PRP similar to T (85.2%). For Prevenar 13, the SP rate was high for each serotype and similar for both groups. All vaccines were well tolerated.

    Conclusions: These study findings confirm the safety and immunogenicity and thus the suitability of this fully liquid hexavalent vaccine for administration in a 2 + 1 schedule.

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