Evaluation of humoral response to heptavalent pneumococcal conjugate vaccine in HIV-infected children. Safety and immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Chilean children Possible prevalence and transmission of acute respiratory tract infections caused by Streptococcus pneumoniae and Haemophilus influenzae among the internally displaced persons in tsunami disaster evacuation camps of Sri Lanka. Vaccination coverage and out-of-sequence vaccinations in rural Guinea-Bissau: an observational cohort study Immunogenicity, Impact on Carriage and Reactogenicity of 10-Valent Pneumococcal Non-Typeable Haemophilus influenzae Protein D Conjugate Vaccine in Kenyan Children Aged 1–4 Years: A Randomized Controlled Trial Pneumococcal Antibody Concentrations of Subjects in Communities Fully or Partially Vaccinated with a Seven-Valent Pneumococcal Conjugate Vaccine Nasopharyngeal Carriage of Pneumococci Four Years after Community-Wide Vaccination with PCV-7 in The Gambia: Long-Term Evaluation of a Cluster Randomized Trial Effects of Community-Wide Vaccination with PCV-7 on Pneumococcal Nasopharyngeal Carriage in The Gambia: A Cluster-Randomized Trial Randomized, Open-Label Study of the Impact of Age on Booster Responses to the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine in Children in India Safety and preliminary immunogenicity of Cuban pneumococcal conjugate vaccine candidate in healthy children: a randomized phase I clinical trial. Safety, reactogenicity and immunogenicity of 2-dose catch-up vaccination with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Malian children in the second year of life: Results from an open study The immunogenicity and safety of pneumococcal conjugate vaccine in human immunodeficiency virus-infected Thai children. Population effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae and non-typeable Haemophilus influenzae in Kilifi, Kenya: findings from cross-sectional carriage studies
OBJECTIVE Invasive pneumococcal disease is a major cause of death in HIV-infected children . The objective of the study was to assess the quantitative antibody response to the seven pneumococcal serotypes of heptavalent pneumococcal conjugate vaccine in a group of HIV-infected children . METHODS Study comprising 40 HIV-infected children aged between 2 and 9 years followed up in a specialized outpatient clinic in São Paulo , Brazil , between 2002 and 2003 .  Enzyme immunoassay ( ELISA ) was used to measure IgG antibody titers against pneumococcus capsule . Antibodies were measured immediately before and 1 month after the second dose of the vaccine . Two response criteria were used : IgG titers > or=1.3 microg/mL in the post-immunization serology and an increase of at least 4or=-fold in post- compared to pre-immunization serology . RESULTS For the first criterion ( > or=1.3 microg/mL ) , 26 ( 65 % ) children had serological response to the vaccine , 12 ( 30 % ) showed post-immunization IgG titers of at least 1.3 microg/mL for all seven serotypes studied . For the second criterion studied ( > or=4-fold increase in post- compared to pre-immunization titers for four serotypes or more ) , serological response was seen in 15 ( 37.5 % ) children . CONCLUSIONS Overall response to the heptavalent pneumococcal conjugate vaccine was adequate , showing a statistically significant increase in the post-immunization geometric mean titers for the seven serotypes studied The safety and immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine ( PHiD-CV , Synflorix ™ ) were assessed in 240 healthy Chilean children r and omized to receive 3 doses of PHiD-CV ( PHiD-CV group ) or hepatitis A vaccine ( HAV control group ) at 2 - 4 - 6 months of age . All were offered 1 HAV dose at 12 months ( outside study ) . The PHiD-CV group received a second HAV dose at 18 - 21 months and PHiD-CV booster at 20 - 23 months . The HAV control group received 2 PHiD-CV catch-up doses at 18 - 21 and 20 - 23 months . Adverse events were recorded and pneumococcal antibody responses and opsonophagocytic activity ( OPA ) were measured . Both PHiD-CV vaccination schedules were well tolerated and immunogenic against the pneumococcal vaccine serotypes and protein D. The reactogenicity of PHiD-CV primary , booster and catch-up doses was in line with previous PHiD-CV studies , although generally higher than with HAV . For each vaccine serotype , the percentage of subjects with antibody concentrations ≥0.2 µg/ml ( GSK 's 22F-inhibition ELISA ) was at least 93.2 % following 3 PHiD-CV primary doses and at least 97.4 % post-booster ; percentages with OPA titers ≥8 were at least 91.7 % post-booster . After 2-dose catch-up , at least 94.3 % of children had antibody concentrations ≥0.2 µg/ml against each serotype except 6B ( 84.3 % ) ; at least 95.2 % had OPA titers ≥8 except against serotypes 1 , 5 and 6B . In conclusion , the safety profiles of 2 PHiD-CV vaccination schedules ( 3-dose primary plus booster and 2-dose catch-up ) were in line with previous studies and PHiD-CV was immunogenic for all 10 vaccine serotypes and protein OBJECTIVE The objective of this prospect i ve study was to investigate the status of acute respiratory tract infections caused by Haemophilus influenzae and Streptococcus pneumoniae in tsunami disaster evacuation camps . METHODS  Nasopharyngeal swabs  ( NP ) of 324 internally displaced persons ( IDP ) in 3 different tsunami disaster evacuation camps of Sri Lanka were collected between March 18th and 20th , 2005 , and analyzed for MIC , beta-lactamase production , serotypes , PCR and pulsed-field gel electrophoresis ( PFGE ) . RESULTS Many IDP had respiratory symptoms and the prevalence of cough and /or sputum was 84 % , 70.5 % and 64.7 % in the three camps . Twenty-one H. influenzae from 20 IDP and 25 S. pneumoniae from 22 IDP were isolated from the NP . All H. influenzae isolates were nontypeable , and 5 were beta-lactamase producing . Seventeen pneumococci were susceptible , 5 showed intermediate resistance and 3 were fully resistant to penicillin G. Molecular analysis showed the 21 H. influenzae strains had 13 PFGE patterns and 25 pneumococci had 16 PFGE patterns . All 4 different PFGE patterns of H. influenzae strains were detected in a few IDP in camps 1 and 3 , and 5 different PFGE patterns of serotype 3 , 22A , 9A , 10A and 11A pneumococci were detected in a few IDP in camps 1 and 3 . CONCLUSION Our data indicate acute respiratory tract infections caused by various types of H. influenzae and S. pneumoniae appear to have been prevalent , some of which were potentially transmitted from person to person in tsunami disaster evacuation camps Objective The WHO aims for 90 % coverage of the Exp and ed Program on Immunization ( EPI ) , which in Guinea-Bissau included BCG vaccine at birth , three doses of diphtheria−tetanus−pertussis vaccine ( DTP ) and oral polio vaccine ( OPV ) at 6 , 10 and 14 weeks and measles vaccine ( MV ) at 9 months when this study was conducted . The WHO assesses coverage by 12 months of age . The sequence of vaccines may have an effect on child mortality , but is not considered in official statistics or assessment s of programme performance . We assessed vaccination coverage and frequency of out-of-sequence vaccinations by 12 and 24 months of age . Design Observational cohort study . Setting and participants The B and i m Health Project 's ( BHP ) rural Health and Demographic Surveillance site covers 258 r and omly selected villages in all regions of Guinea-Bissau . Villages are visited biannually and vaccination cards inspected to ascertain vaccination status . Between 2003 and 2009 vaccination status by 12 months of age was assessed for 5806 children aged 12–23 months ; vaccination status by 24 months of age was assessed for 3792 children aged 24–35 months . Outcome measures Coverage of EPI vaccinations and frequency of out-of-sequence vaccinations . Results Half of 12-month-old children and 65 % of 24-month-old children had completed all EPI vaccinations . Many children received vaccines out of sequence : by 12 months of age 54 % of BCG-vaccinated children had received DTP with or before BCG and 28 % of measles-vaccinated children had received DTP with or after MV . By 24 months of age the proportion of out-of-sequence vaccinations was 58 % and 35 % , respectively , for BCG and MV . Conclusions In rural Guinea-Bissau vaccination coverage by 12 months of age was low , but continued to increase beyond 12 months of age . More than half of all children received vaccinations out of sequence . This highlights the need to improve vaccination services Background The impact on carriage and optimal schedule for primary vaccination of older children with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine ( PHiD-CV )  are unknown . Methods 600 Kenyan children aged 12–59 months were vaccinated at days 0 , 60 and 180 in a double-blind r and omized controlled trial according to the following vaccine sequence : Group A : PHiD-CV , PHiD-CV , diphtheria/tetanus/acellular pertussis vaccine ( DTaP ) ; Group B : PHiD-CV , DTaP , PHiD-CV ; Group C : hepatitis A vaccine ( HAV ) , DTaP , HAV . Nasopharyngeal carriage of Streptococcus pneumoniae was measured at five timepoints . In 375 subjects , serotype-specific responses were measured by 22F-inhibition ELISA and opsonophagocytic killing assays ( OPA ) one month after vaccination . Results Following one dose of PHiD-CV , > 90 % of recipients developed IgG≥0.35 µg/mL to serotypes 1 , 4 , 5 , 7F , 9V and 18C and OPA≥8 to serotypes 4 , 7F , 9V , 18C , 23F . After a second dose > 90 % of recipients had IgG≥0.35 µg/mL to all vaccine serotypes and OPA≥8 to all vaccine serotypes except 1 and 6B . At day 180 , carriage of vaccine-type pneumococci was 21 % in recipients of two doses of PHiD-CV ( Group A ) compared to 31 % in controls ( p = 0.04 ) . Fever after dose 1 was reported by 41 % of PHiD-CV recipients compared to 26 % of HAV recipients ( p<0.001 ) . Other local and systemic adverse experiences were similar between groups . Conclusions Vaccination of children aged 12–59 months with two doses of PHiD-CV two to six months apart was immunogenic , reduced vaccine-type pneumococcal carriage and was well-tolerated . Administration of PHiD-CV would be expected to provide effective protection against vaccine-type disease . Trial Registration Clinical Trials.gov Background A recent trial with PCV-7 in a rural Gambian community showed reduced vaccine-type pneumococcal carriage in fully vaccinated compared with control communities . We measured pneumococcal polysaccharide antibody concentrations in this trial to underst and further the mechanisms underlying the observed changes . Methods A single-blind , cluster-r and omized ( by village ) trial was conducted in 21 Gambian villages . In 11 villages , all residents received PCV-7 ( Vaccine group ) ; in 10 control villages only children < 30 months old or those born during the study received PCV-7 .  Subjects over the age of 30 months resident in vaccine villages received a single dose of PCV-7 whilst those in control villages received a single dose of a serogroup C meningococcal conjugate vaccine .  Serum antibody concentrations against specific pneumococcal polysaccharides were measured in approximately 200 age-stratified subjects before , 4–6 , 12 and 24 months following vaccination . Results Baseline pneumococcal antibody concentrations were generally high and increased with age up to 10 years . One dose of PCV-7 increased geometric mean antibody concentrations ( GMC ) in vaccinated versus control villages for vaccine serotypes 6B and 18C , and 4 and 18C , in the young ( under 5 years ) and older age groups ( 5 + years ) respectively . There were significantly higher proportions of subjects in the vaccinated than in the control communities with an antibody concentration believed to protect against carriage ( > 5.0 µg/mL ) for all but serotype 9V of the PCV-7 serotypes in the older group , but not in the younger age group . Conclusion Higher antibodies in vaccinated communities provide an explanation for the lower pneumococcal carriage rates in fully vaccinated compared to control communities . Trial Registration Controlled-Trials.com IS RCT N51695599 51695599 Background A village-r and omized trial of a seven-valent pneumococcal-conjugate-vaccine ( PCV-7 ) conducted in rural Gambia showed a decrease of vaccine-type ( VT ) and a non-significant increase in non-vaccine-type ( NVT ) nasopharyngeal carriage of pneumococci two years after vaccination . Here , we report findings four years after vaccination . Methods PCV-7 was given to all children below 30 months of age enrolled in the trial and to those born during its course in all study villages . Villages were r and omized ( older children and adults ) to receive  PCV-7 ( wholly vaccinated villages ) or  serogroup-C-meningococcal-conjugate-vaccine  ( partly vaccinated villages ) . Cross-sectional surveys ( CSS ) to collect nasopharyngeal swabs were conducted before and at various intervals after vaccination . Sixteen of these r and omized villages ( 8 wholly vaccinated and 8 partly vaccinated ) participated in a CSS conducted four years after vaccination started . Results Four years after vaccination , the prevalence of VT pneumococcal carriage was slightly higher in partly than in wholly vaccinated villages [ 6.4 % versus 3.9 % ( p = 0.120 ) ] compared to 24.4 % in the pre-vaccination CSS ( p<0.001 ) . Prevalence of NVT four years after vaccination was similar between study groups [ 32.7 % versus 29.8 % ( p = 0.392 ) , respectively ] compared to 51.1 % in the pre-vaccination CSS ( p<0.001 ) . Four years after vaccination started , lower prevalence of serotype 6A was detected in wholly vaccinated than in partly vaccinated villages ( 1.6 % versus 3.5 % , p = 0.093 ) whilst the prevalence of serotype 19A was similar between groups ( 2.9 % versus 2.5 % , p = 0.779 ) . The most prevalent serotype 19A clone was ST 847 . The most prevalent serotype 6A clone before vaccination was ST3324 whilst after vaccination ST913 and ST1737 predominated . Fourteen out of 26 STs detected among the serotype 6A isolates were new while no new 19A serotype ST was found . Conclusions The decline in prevalence of VT pneumococci seen shortly after PCV-7 vaccination was sustained four years later with only a small difference between study arms . No significant serotype replacement was detected . Trial Registration Clinical Trials.gov IS RCT In a cluster-r and omized trial conducted in Gambian villages , Anna Roca and colleagues find that vaccination of children with pneumococcal conjugate vaccines reduced vaccine-type pneumococcal carriage even among nonvaccinated older children and adults ABSTRACT In this phase III , open-label , multicenter , and descriptive study in India , children primed with 3 doses ( at ages 6 , 10 , and 14 weeks ) of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine ( PHiD-CV ) were r and omized ( 1:1 ) to receive a booster dose at 9 to 12 ( early booster ) or 15 to 18 months old  ( late booster ) in order to evaluate impact of age at booster . We also evaluated a 2-dose catch-up vaccination plus an experimental booster dose in unprimed children age 12 to 18 months . The early booster , late booster , and catch-up vaccinations were administered to 74 , 95 , and 87 children , respectively ; 66 , 71 , and 81 children , respectively , were included in the immunogenicity according-to- protocol cohort . One month postbooster , for each PHiD-CV serotype , ≥95.2 % ( early booster ) and ≥93.8 % ( late booster ) of the children had antibody concentrations of ≥0.2 μg/ml ; ≥96.7 % and ≥93.0 % , respectively , had opsonophagocytic activity ( OPA ) titers of ≥8 . The postbooster antibody geometric mean concentrations ( GMCs ) were in similar ranges for early and late boosters ; the OPA titers appeared to be lower for most PHiD-CV serotypes ( except 6B and 19F ) after the early booster . After dose 2 and postbooster , for each PHiD-CV serotype , ≥88.6 % and ≥96.3 % , respectively , of the catch-up immunogenicity according-to- protocol cohort had antibody concentrations of ≥0.2 μg/ml ; ≥71.4 % and ≥90.6 % , respectively , had OPA titers of ≥8 . At least 1 serious adverse event was reported by 2 children in the early booster ( skin infection and gastroenteritis ) and 1 child in the catch-up group ( febrile convulsion and urinary tract infection ) ; all were resolved , and none were considered by the investigators to be vaccine related . PHiD-CV induced robust immune responses regardless of age at booster . Booster vaccination following 2 catch-up doses induced robust immune responses indicative of effective priming and immunological memory . ( These studies have been registered at www . clinical trials.gov under registration no. NCT01030822 and NCT00814710 ; a protocol summary is available at www.gsk- clinical study register.com [ study ID 112909 ] ) A new heptavalent conjugate vaccine ( PCV7-TT ) is under development in Cuba .  PCV7-TT contains 2 μg of serotypes 1 , 5 , 14 , 18C , 19F , 23F and 4 μg of 6B , each one conjugated to tetanus toxoid ( TT ) . This vaccine was design ed with the serotypes that cause most invasive pneumococcal diseases ( IPD ) worldwide . In the present study , we investigated the safety and explored the immunogenicity of PCV7-TT during a controlled , r and omized and double blind clinical trial phase I in 4 - 5-year-old children .  PCV7-TT  was well tolerated and as safe as Synflorix used as control vaccine . Following a single-dose vaccination , all individual serotypes included in PCV7-TT  induced statistically significant increase of IgG GMC and OPA GMT . These are the first clinical results of PCV7-TT in children and they pave the way toward next clinical trials in children and infants . This clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173 Pneumonia is still the leading cause of death among African children with pneumococcal serotypes 1 and 5 being dominant in the below 5 y of age group . The present study assessed the safety , reactogenicity and immunogenicity of a 2-dose catch-up vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae Protein D conjugate vaccine ( PHiD-CV ) in Malian children . This phase III , open-label study ( NCT00985465 ) was conducted in Ouelessebougou , Mali , between November 2009 and July 2010 . The study population consisted of PHiD-CV unprimed Malian children previously enrolled in the control group of study NCT00678301 receiving a 2-dose catch-up vaccination with PHiD-CV in the second year of life . Adverse events were recorded following each PHiD-CV dose . Antibody responses and opsonophagocytic activity ( OPA ) were measured pre-vaccination and after the second PHiD-CV catch-up dose . Swelling and fever ( axillary temperature ≥ 37.5 ° C ) were the most frequently reported solicited symptoms following either PHiD-CV dose . Few grade 3 solicited symptoms were reported . Large swelling reactions and serious adverse events were not reported . Post-catch-up vaccination , for each vaccine pneumococcal serotype , at least 94.7 % of subjects had antibody concentrations ≥ 0.2 μg/ml , except for serotypes 6B ( 82.5 % ) and 23F ( 87.7 % ) . At least 94.0 % of subjects had OPA titres ≥ 8 , except for serotype 19F ( 89.4 % ) . The geometric mean concentration for antibodies against protein D was 839.3 ( 95 % CI : 643.5 - 1094.6 ) EL.U/ml . Two-dose PHiD-CV catch-up regimen in the second year of life was well-tolerated and immunogenic for all vaccine pneumococcal serotypes and NTHi protein D when administered to Malian BACKGROUND HIV-infected children have high risk of invasive pneumococcal disease ( IPD ) despite receiving highly active antiretroviral therapy ( HAART ) . This study aim ed to determine the immunogenicity and safety of a 7-valent pneumococcal conjugate vaccine ( PCV-7 ) in Thai HIV-infected children compared to HIV-exposed uninfected children . METHODS A prospect i ve study was conducted among children 2 months to 9 years . The number of PCV-7 doses depended upon age and HIV status ; 2 - 6 months of age : 3 doses ; 7 - 23 months of age : 2 doses ; HIV-infected child ≥24 months : 2 doses and HIV-exposed child ≥24 months : 1 dose . Serotype-specific pneumococcal IgG antibody concentrations were measured at baseline and 28 days after complete vaccination . The primary end point was the proportion of children who achieved serotype-specific IgG antibody concentration at a cut off level ≥0.35 μg/mL. Secondary end points were a 4-fold increase in serotype-specific IgG antibody , rates of adverse events and predictors for seroconversion among HIV-infected children . RESULTS Fifty-nine HIV-infected and 30 HIV-exposed children were enrolled . The median ( IQR ) age was 97 ( 67 - 111 ) and 61 months ( 51 - 73 ) , respectively ( p<0.001 ) . Among HIV-infected children , current and nadir CD4 counts were 1,079 cell/mm(3 ) and 461 cell/mm(3 ) , respectively . The proportion of children who achieved pneumococcal IgG ≥0.35 μg/mL was in the range of 85 - 98 % in HIV-infected and 83 - 100 % in HIV-exposed children depending on serotype . The lowest response was to serotype 6B in both groups . The 4-fold increase in serotype-specific IgG concentrations was similar between HIV-infected and HIV-exposed groups , except for serotype 9V ( p=0.027 ) . HIV-infected children who had a history of AIDS  had a lower antibody response to serotype 23F ( p=0.025 ) . Seven ( 12 % ) HIV-infected children had a grade 3 local reaction . CONCLUSION PCV-7 is highly immunogenic and safe among HIV-infected children treated with HAART . The use of the pneumococcal conjugate vaccine among HIV-infected children is encouraged in order to prevent IPD Summary Background The effect of 7-valent pneumococcal conjugate vaccine ( PCV ) in developed countries was enhanced by indirect protection of unvaccinated individuals , mediated by reduced nasopharyngeal carriage of vaccine-serotype pneumococci . The potential indirect protection of 10-valent PCV ( PCV10 ) in a developing country setting is unknown . We sought to estimate the effectiveness of introduction of PCV10 in Kenya against carriage of vaccine serotypes and its effect on other bacteria . Methods PCV10 was introduced into the infant vaccination programme in Kenya in January , 2011 , accompanied by a catch-up campaign in Kilifi County for children aged younger than 5 years . We did annual cross-sectional carriage studies among an age-stratified , r and om population sample in the 2 years before and 2 years after PCV10 introduction . A nasopharyngeal rayon swab specimen was collected from each participant and was processed in accordance with WHO recommendations . Prevalence ratios of carriage before and after introduction of PCV10 were calculated by log-binomial regression . Findings About 500 individuals were enrolled each year ( total n=2031 ) . Among children younger than 5 years , the baseline ( 2009–10 ) carriage prevalence was 34 % for vaccine-serotype Streptococcus pneumoniae , 41 % for non-vaccine-serotype Streptococcus pneumoniae , and 54 % for non-typeable Haemophilus influenzae . After PCV10 introduction ( 2011–12 ) , these percentages were 13 % , 57 % , and 40 % , respectively . Adjusted prevalence ratios were 0·36 ( 95 % CI 0·26–0·51 ) , 1·37 ( 1·13–1·65 ) , and 0·62 ( 0·52–0·75 ) , respectively . Among individuals aged 5 years or older , the adjusted prevalence ratios for vaccine-serotype and non-vaccine-serotype S pneumoniae carriage were 0·34 ( 95 % CI 0·18–0·62 ) and 1·13 ( 0·92–1·38 ) , respectively . There was no change in prevalence ratio for Staphylococcus aureus ( adjusted prevalence ratio for those < 5 years old 1·02 , 95 % CI 0·52–1·99 , and for those ≥5 years old 0·90 , 0·60–1·35 ) . Interpretation After programmatic use of PCV10 in Kilifi , carriage of vaccine serotypes was reduced by two-thirds both in children younger than 5 years and in older individuals . These findings suggest that PCV10 introduction in Africa will have substantial indirect effects on invasive pneumococcal disease . Funding GAVI Alliance and Wellcome Trust
INTRODUCTION Pneumococcal conjugate vaccine ( PCV ) is included in the World Health Organization 's routine immunization schedule and is recommended by WHO for vaccination in high-risk children up to 60 months .
However , many countries do not recommend vaccination in older age groups , nor have donors committed to supporting extended age group vaccination .
To better inform decision-making , this systematic review examines the direct impact of extended age group vaccination in children over 12 months in low and middle income countries .