Taneli Puumalainen - Academia.edu (original) (raw)

Papers by Taneli Puumalainen

Pediatric Infectious Disease Journal, 2003

Antibody responses to pneumococcal conjugate vaccines may vary when administered in different pop... more Antibody responses to pneumococcal conjugate vaccines may vary when administered in different populations or epidemiologic settings. Understanding the causes and significance of this variation could help to determine the number of doses and timing required for protection against pneumococcal diseases in each country. This report compares antibody responses to aluminum-adjuvanted and nonadjuvanted mixed carrier 11-valent diphtheria- or tetanus-conjugated pneumococcal vaccine (11-PncTD) formulations when given at 6, 10 and 14 weeks and 9 months of age to Filipino infants (n = 51) and at 2, 4, 6 and 12 months of age to Finnish (n = 127) and Israeli (n = 124) infants. The study populations differ in their natural exposure to pneumococcus and risk factors for pneumococcal carriage and disease. Filipino and Israeli infants had slightly but significantly higher prevaccination geometric mean concentration (GMC) of antibodies than did the Finnish infants. After three doses of aluminum-adjuvanted 11-PncTD vaccine, the Filipino infants had 1.8 to 6.7 and 1.5 to 5.0 times higher GMC than the Finnish and Israeli infants, respectively, against pneumococcal serotypes conjugated to tetanus protein. The GMC of serotypes conjugated to diphtheria toxoid was 1.3 to 3.0 and 0.7 to 2.0 times the GMC in Finnish and Israeli infants, respectively. The nonadjuvanted vaccine formulation induced generally lower GMCs. The antibody responses to the tetanus-conjugated polysaccharides were considerably higher in the Filipino than in the Finnish or Israeli infants. This may be a result of several factors including the priming effect of tetanus toxoid given to pregnant women, early pneumococcal nasopharyngeal acquisition and genetic differences among populations.

Journal of Infectious Diseases, 2003

The aluminium-adjuvanted 11-valent pneumococcal conjugate vaccine containing polysaccharides 1, 4... more The aluminium-adjuvanted 11-valent pneumococcal conjugate vaccine containing polysaccharides 1, 4, 5, 7F, 9V, 19F, and 23F (coupled to tetanus protein) and polysaccharides 3, 6B, 14, and 18C (coupled to diphtheria toxoid) elicits high antibody concentrations in Filipino infants when given at ages 6, 10, and 14 weeks and 9 months simultaneously with the national vaccination program. We evaluated functional activity of these antibodies by using a viable cell opsonophagocytic assay (OPA). The OPA titers correlated ( -0.74) r p 0.53 with the respective antibody concentrations. The geometric mean OPA titers after 3 vaccine doses were 276.9 (serotype 4), 12.3 (serotype 6B), 46.0 (serotype 14), 119.

Journal of Infectious Diseases, 2004

In Filipino infants, 1 dose of an adjuvanted, 11-valent pneumococcal conjugate vaccine (serotypes... more In Filipino infants, 1 dose of an adjuvanted, 11-valent pneumococcal conjugate vaccine (serotypes 1, 4, 5, 7F, 9V, 19F, and 23F conjugated to tetanus protein; and serotypes 3, 6B, 14, and 18C conjugated to diphtheria toxoid) administered alone at age 18 weeks (11PncTD1) elicited similar antibody concentrations at age 9 months as those elicited by 3 doses (11PncTD3) administered concomitantly with national program vaccines, at ages 6, 10, and 14 weeks. Geometric mean antibody concentrations ranged from 0.36 mg/mL (for serotype 18C) to 5.81 mg/mL (for serotype 4), for the 11PncTD1 vaccine, and from 0.32 mg/mL (for serotype 18C) to 5.01 mg/mL (for serotype 19F), for the 11PncTD3 vaccine. The proportion of infants with threshold antibody concentrations у0.35 mg/mL was also similar (ranges, 55.6%-100% for the 11PncTD1 vaccine and 42.9%-100% for the 11PncTD3 vaccine). The functional activity of antibodies expressed as opsonophagocytic activity titers was similar in the 11PncTD1 and 11PncTD3 groups. This finding is an important one for countries with financial constraints and high pneumococcal disease burden.

Pediatric Infectious Disease Journal, 2009

Pneumococcus is a leading cause of childhood pneumonia worldwide. Pneumococcal conjugate vaccines... more Pneumococcus is a leading cause of childhood pneumonia worldwide. Pneumococcal conjugate vaccines (PCV) have demonstrated efficacy against childhood invasive pneumococcal disease (IPD) and pneumonia in the United States and Africa. No information is available from Asia on the impact of PCV on childhood pneumonia. We conducted a randomized, placebo-controlled, double-blind trial in Bohol, the Philippines (ISRCTN 62323832). Children 6 weeks to <6 months of age were randomly allocated to receive 3 doses of either an 11-valent PCV (11PCV, sanofi pasteur, Lyon, France) or a saline placebo, with a minimum interval of 4 weeks between doses to determine vaccine efficacy (VE) against the primary outcome of a child experiencing first episode of community-acquired radiologically defined pneumonia in the first 2 years of life. Secondary end points were clinical pneumonia, IPD, safety, and immunogenicity. Twelve thousand one hundred ninety-one children were enrolled. By per protocol (PP) analysis, 93 of 6013 fully vaccinated 11PCV recipient children had a first episode of radiologic pneumonia compared with 120 of 6018 placebo recipients. VE against radiologically defined pneumonia for the PP cohort of children 3 to 23 months old was 22.9% (95% CI: -1.1, 41.2; P = 0.06), for the prespecified subgroups of children 3 to 11 months of age, 34.0% (95% CI: 4.8, 54.3; P = 0.02), and of those 12 to 23 months old, 2.7% (95% CI: -43.5, 34.0; P = 0.88). By intent-to-treat (ITT) analysis, 119 of 6097 11PCV recipient children had an episode of radiologic pneumonia compared with 141 of 6094 placebo recipients. VE against radiologic pneumonia for the ITT cohort of children <2 years old was 16.0% (95% CI -7.3, 34.2; P = 0.16), for a subgroup of children <12 months of age, 19.8% (95% CI: -8.8, 40.8; P = 0.15). VE against clinical pneumonia by PP was not significant (VE 0.1%; 95% CI -9.4, 8.7; P = 0.99). IPD was rare: only 3 cases of IPD due to vaccine serotypes were observed during the study. 11PCV was immunogenic and well tolerated. Among 11PCV recipients, a small excess of serious adverse respiratory events was observed in the first 28 days after the first and second dose of vaccine, and of nonrespiratory events after the first dose. An excess of pneumonia episodes in 11PCV recipients in the month following the second dose of vaccination was the principal reason for lower VE by ITT analysis than by PP analysis. In PP analysis, a 22.9% reduction of community-acquired radiologically confirmed pneumonia in children younger than 2 years of age in the 11-valent tetanus-diphtheria toxoid-conjugated PCV vaccinated group was observed; a reduction similar as observed in other PCV trials. We could not demonstrate any VE against clinical pneumonia. Our finding confirms for the first time that in a low-income, low-mortality developing country in Asia, at least one-fifth of radiologically confirmed pneumonia is caused by pneumococcus, and thus preventable by PCV. Whether PCV should be included in national program in such settings, however, depends on careful country specific disease burden measurement and cost-effectiveness calculation.

BMC Infectious Diseases, 2003

Background: An 11-valent pneumococcal conjugate vaccine could provide significantly larger reduct... more Background: An 11-valent pneumococcal conjugate vaccine could provide significantly larger reduction in pneumococcal disease burden than the currently available 7-valent vaccine formulation in many countries.

Pediatric Infectious Disease Journal, 2002

... PUUMALAINEN, TANELI MD; ZETA-CAPEDING, M. ROSE MD; KÄYHTY, HELENA PhD; LUCERO, MARILLA G. MD;... more ... PUUMALAINEN, TANELI MD; ZETA-CAPEDING, M. ROSE MD; KÄYHTY, HELENA PhD; LUCERO, MARILLA G. MD; AURANEN, KARI PhD; LEROY, ODILE MD*; NOHYNEK,HANNA MD. Article Outline. Collapse Box Author Information. ...

BMC Infectious Diseases, 2008

Background The World Health Organization's (WHO) case definition for childhood pneumonia, compose... more Background The World Health Organization's (WHO) case definition for childhood pneumonia, composed of simple clinical signs of cough, difficult breathing and fast breathing, is widely used in resource poor settings to guide management of acute respiratory infections. The definition is also commonly used as an entry criteria or endpoint in different intervention and disease burden studies. Methods A group of paediatricians conducted a retrospective review of clinical and laboratory data including C-reactive protein concentration and chest radiograph findings among Filipino children hospitalised in the Bohol Regional Hospital who were enrolled in a pneumococcal vaccine efficacy study and had an episode of respiratory disease fulfilling the WHO case definition for clinical pneumonia. Our aim was to evaluate which disease entities the WHO definition actually captures and what is the probable aetiology of respiratory infections among these episodes diagnosed in this population. Results Among the 12,194 children enrolled to the vaccine study we recorded 1,195 disease episodes leading to hospitalisation which fulfilled the WHO criteria for pneumonia. In total, 34% of these episodes showed radiographic evidence of pneumonia and 11% were classified as definitive or probable bacterial pneumonia. Over 95% of episodes of WHO-defined severe pneumonia (with chest indrawing) had an acute lower respiratory infection as final diagnosis whereas 34% of those with non-severe clinical pneumonia had gastroenteritis or other non-respiratory infection as main cause of hospitalisation. Conclusion The WHO definition for severe pneumonia shows high specificity for acute lower respiratory infection and provides a tool to compare the total burden of lower respiratory infections in different settings. Trial registration ISRCTN62323832

Pediatric Infectious Disease Journal, 2003

Antibody responses to pneumococcal conjugate vaccines may vary when administered in different pop... more Antibody responses to pneumococcal conjugate vaccines may vary when administered in different populations or epidemiologic settings. Understanding the causes and significance of this variation could help to determine the number of doses and timing required for protection against pneumococcal diseases in each country. This report compares antibody responses to aluminum-adjuvanted and nonadjuvanted mixed carrier 11-valent diphtheria- or tetanus-conjugated pneumococcal vaccine (11-PncTD) formulations when given at 6, 10 and 14 weeks and 9 months of age to Filipino infants (n = 51) and at 2, 4, 6 and 12 months of age to Finnish (n = 127) and Israeli (n = 124) infants. The study populations differ in their natural exposure to pneumococcus and risk factors for pneumococcal carriage and disease. Filipino and Israeli infants had slightly but significantly higher prevaccination geometric mean concentration (GMC) of antibodies than did the Finnish infants. After three doses of aluminum-adjuvanted 11-PncTD vaccine, the Filipino infants had 1.8 to 6.7 and 1.5 to 5.0 times higher GMC than the Finnish and Israeli infants, respectively, against pneumococcal serotypes conjugated to tetanus protein. The GMC of serotypes conjugated to diphtheria toxoid was 1.3 to 3.0 and 0.7 to 2.0 times the GMC in Finnish and Israeli infants, respectively. The nonadjuvanted vaccine formulation induced generally lower GMCs. The antibody responses to the tetanus-conjugated polysaccharides were considerably higher in the Filipino than in the Finnish or Israeli infants. This may be a result of several factors including the priming effect of tetanus toxoid given to pregnant women, early pneumococcal nasopharyngeal acquisition and genetic differences among populations.

Journal of Infectious Diseases, 2003

The aluminium-adjuvanted 11-valent pneumococcal conjugate vaccine containing polysaccharides 1, 4... more The aluminium-adjuvanted 11-valent pneumococcal conjugate vaccine containing polysaccharides 1, 4, 5, 7F, 9V, 19F, and 23F (coupled to tetanus protein) and polysaccharides 3, 6B, 14, and 18C (coupled to diphtheria toxoid) elicits high antibody concentrations in Filipino infants when given at ages 6, 10, and 14 weeks and 9 months simultaneously with the national vaccination program. We evaluated functional activity of these antibodies by using a viable cell opsonophagocytic assay (OPA). The OPA titers correlated ( -0.74) r p 0.53 with the respective antibody concentrations. The geometric mean OPA titers after 3 vaccine doses were 276.9 (serotype 4), 12.3 (serotype 6B), 46.0 (serotype 14), 119.

Journal of Infectious Diseases, 2004

In Filipino infants, 1 dose of an adjuvanted, 11-valent pneumococcal conjugate vaccine (serotypes... more In Filipino infants, 1 dose of an adjuvanted, 11-valent pneumococcal conjugate vaccine (serotypes 1, 4, 5, 7F, 9V, 19F, and 23F conjugated to tetanus protein; and serotypes 3, 6B, 14, and 18C conjugated to diphtheria toxoid) administered alone at age 18 weeks (11PncTD1) elicited similar antibody concentrations at age 9 months as those elicited by 3 doses (11PncTD3) administered concomitantly with national program vaccines, at ages 6, 10, and 14 weeks. Geometric mean antibody concentrations ranged from 0.36 mg/mL (for serotype 18C) to 5.81 mg/mL (for serotype 4), for the 11PncTD1 vaccine, and from 0.32 mg/mL (for serotype 18C) to 5.01 mg/mL (for serotype 19F), for the 11PncTD3 vaccine. The proportion of infants with threshold antibody concentrations у0.35 mg/mL was also similar (ranges, 55.6%-100% for the 11PncTD1 vaccine and 42.9%-100% for the 11PncTD3 vaccine). The functional activity of antibodies expressed as opsonophagocytic activity titers was similar in the 11PncTD1 and 11PncTD3 groups. This finding is an important one for countries with financial constraints and high pneumococcal disease burden.

Pediatric Infectious Disease Journal, 2009

Pneumococcus is a leading cause of childhood pneumonia worldwide. Pneumococcal conjugate vaccines... more Pneumococcus is a leading cause of childhood pneumonia worldwide. Pneumococcal conjugate vaccines (PCV) have demonstrated efficacy against childhood invasive pneumococcal disease (IPD) and pneumonia in the United States and Africa. No information is available from Asia on the impact of PCV on childhood pneumonia. We conducted a randomized, placebo-controlled, double-blind trial in Bohol, the Philippines (ISRCTN 62323832). Children 6 weeks to <6 months of age were randomly allocated to receive 3 doses of either an 11-valent PCV (11PCV, sanofi pasteur, Lyon, France) or a saline placebo, with a minimum interval of 4 weeks between doses to determine vaccine efficacy (VE) against the primary outcome of a child experiencing first episode of community-acquired radiologically defined pneumonia in the first 2 years of life. Secondary end points were clinical pneumonia, IPD, safety, and immunogenicity. Twelve thousand one hundred ninety-one children were enrolled. By per protocol (PP) analysis, 93 of 6013 fully vaccinated 11PCV recipient children had a first episode of radiologic pneumonia compared with 120 of 6018 placebo recipients. VE against radiologically defined pneumonia for the PP cohort of children 3 to 23 months old was 22.9% (95% CI: -1.1, 41.2; P = 0.06), for the prespecified subgroups of children 3 to 11 months of age, 34.0% (95% CI: 4.8, 54.3; P = 0.02), and of those 12 to 23 months old, 2.7% (95% CI: -43.5, 34.0; P = 0.88). By intent-to-treat (ITT) analysis, 119 of 6097 11PCV recipient children had an episode of radiologic pneumonia compared with 141 of 6094 placebo recipients. VE against radiologic pneumonia for the ITT cohort of children <2 years old was 16.0% (95% CI -7.3, 34.2; P = 0.16), for a subgroup of children <12 months of age, 19.8% (95% CI: -8.8, 40.8; P = 0.15). VE against clinical pneumonia by PP was not significant (VE 0.1%; 95% CI -9.4, 8.7; P = 0.99). IPD was rare: only 3 cases of IPD due to vaccine serotypes were observed during the study. 11PCV was immunogenic and well tolerated. Among 11PCV recipients, a small excess of serious adverse respiratory events was observed in the first 28 days after the first and second dose of vaccine, and of nonrespiratory events after the first dose. An excess of pneumonia episodes in 11PCV recipients in the month following the second dose of vaccination was the principal reason for lower VE by ITT analysis than by PP analysis. In PP analysis, a 22.9% reduction of community-acquired radiologically confirmed pneumonia in children younger than 2 years of age in the 11-valent tetanus-diphtheria toxoid-conjugated PCV vaccinated group was observed; a reduction similar as observed in other PCV trials. We could not demonstrate any VE against clinical pneumonia. Our finding confirms for the first time that in a low-income, low-mortality developing country in Asia, at least one-fifth of radiologically confirmed pneumonia is caused by pneumococcus, and thus preventable by PCV. Whether PCV should be included in national program in such settings, however, depends on careful country specific disease burden measurement and cost-effectiveness calculation.

BMC Infectious Diseases, 2003

Background: An 11-valent pneumococcal conjugate vaccine could provide significantly larger reduct... more Background: An 11-valent pneumococcal conjugate vaccine could provide significantly larger reduction in pneumococcal disease burden than the currently available 7-valent vaccine formulation in many countries.

Pediatric Infectious Disease Journal, 2002

... PUUMALAINEN, TANELI MD; ZETA-CAPEDING, M. ROSE MD; KÄYHTY, HELENA PhD; LUCERO, MARILLA G. MD;... more ... PUUMALAINEN, TANELI MD; ZETA-CAPEDING, M. ROSE MD; KÄYHTY, HELENA PhD; LUCERO, MARILLA G. MD; AURANEN, KARI PhD; LEROY, ODILE MD*; NOHYNEK,HANNA MD. Article Outline. Collapse Box Author Information. ...

BMC Infectious Diseases, 2008

Background The World Health Organization's (WHO) case definition for childhood pneumonia, compose... more Background The World Health Organization's (WHO) case definition for childhood pneumonia, composed of simple clinical signs of cough, difficult breathing and fast breathing, is widely used in resource poor settings to guide management of acute respiratory infections. The definition is also commonly used as an entry criteria or endpoint in different intervention and disease burden studies. Methods A group of paediatricians conducted a retrospective review of clinical and laboratory data including C-reactive protein concentration and chest radiograph findings among Filipino children hospitalised in the Bohol Regional Hospital who were enrolled in a pneumococcal vaccine efficacy study and had an episode of respiratory disease fulfilling the WHO case definition for clinical pneumonia. Our aim was to evaluate which disease entities the WHO definition actually captures and what is the probable aetiology of respiratory infections among these episodes diagnosed in this population. Results Among the 12,194 children enrolled to the vaccine study we recorded 1,195 disease episodes leading to hospitalisation which fulfilled the WHO criteria for pneumonia. In total, 34% of these episodes showed radiographic evidence of pneumonia and 11% were classified as definitive or probable bacterial pneumonia. Over 95% of episodes of WHO-defined severe pneumonia (with chest indrawing) had an acute lower respiratory infection as final diagnosis whereas 34% of those with non-severe clinical pneumonia had gastroenteritis or other non-respiratory infection as main cause of hospitalisation. Conclusion The WHO definition for severe pneumonia shows high specificity for acute lower respiratory infection and provides a tool to compare the total burden of lower respiratory infections in different settings. Trial registration ISRCTN62323832