Nasopharyngeal Carriage Study in Healthy Kenyan Toddlers
A Prospective Study to Assess the Nasopharyngeal Carriage of Streptococcus Pneumoniae (SPn), Long Term Safety and Immune Persistence in Healthy Kenyan PCV-Primed Toddlers (12-15 Months of Age) Who Received a Whole Cell Pneumococcal Vaccine (PATH-wSP) Compared to Controls
調査の概要
状態
条件
詳細な説明
This study enrolled healthy Kenyan toddlers (12-15 months of age) who participated in the randomized control trial of VAC-010 (NCT02097472), as well as healthy toddlers aged 12 to 15 months who had not participated in the VAC-010 Study. All participants must have received a primary dose of pneumococcal conjugate vaccine (PCV) per local practice prior to enrollment in either VAC-010 or VAC-011. No treatments were administered during this study.
The study consisted of the following four groups:
Participants who were randomized in study VAC-010 (2:2:1 ratio), defined according to the treatment received in VAC-010:
- 1. PATH-wSP + Booster
- 2. PATH-wSP Only
- 3. Booster Only
Participants who did not participate in VAC-010:
- 4. No Intervention
Each group consisted of 2 cohorts of participants, Cohort 1 (300 µg PATH-wSP) and Cohort 2 (600 µg PATH-wSP). Enrollment into Cohorts 1 and 2 occurred sequentially; participants in groups 3 and 4 who did not receive PATH-wSP were also enrolled over time and allocated into one of the two cohorts (300 and 600 µg) in order to control for potential seasonal variation in the NPC of S. pneumoniae.
Each participant completed a total of 5 scheduled visits. For toddlers enrolled simultaneously in VAC-010, visits corresponded to enrollment (Baseline) and 4, 8, 12, and 24 weeks post final vaccination in VAC-010. For toddlers in the No Intervention group, the first visit corresponded to Baseline and the second to fifth visits corresponded to 12, 16, 20, and 32 weeks later. Nasopharyngeal swabs were taken at each visit following World Health Organization (WHO) guidelines for analysis of nasopharyngeal burden.
Treatments received during VAC-010 included:
- PATH-wSP: Streptococcus pneumoniae whole cell vaccine with aluminum hydroxide adjuvant
- Synflorix™ booster vaccine: pneumococcal polysaccharide conjugate vaccine (adsorbed)
- Pentavac booster vaccine: diphtheria, tetanus, pertussis (Whole Cell), hepatitis B (recombinant deoxyribonucleic acid [rDNA]) and Haemophilus influenzae type b conjugate vaccine (adsorbed).
- Saline control
研究の種類
入学 (実際)
連絡先と場所
研究場所
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Kisumu、ケニア、40100
- Kenya Medical Research Institute/Walter Reed Project
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
説明
Inclusion Criteria:
- For Toddlers Enrolled in VAC-010 (NCT02097472):
- Randomization in VAC-010.
- Subject's parent must provide voluntary written informed consent for subject to participate in the study, is fully capable of comprehending and complying with study requirements and procedures, able and willing to return for all scheduled follow-up visits, and has expressed availability for the required study period, with access to a consistent means of telephone contact. An illiterate parent will require an impartial witness to be present during consenting process to include discussing the consent form, verbal consent and thumb-printing.
- Subject has not completed his or her final vaccination in VAC-010.
For Toddlers NOT Enrolled in VAC-010 (PCV-primed-only cohort):
- Healthy Kenyan toddlers between 12 to 15 (inclusive) months of age who have completed their primary Expanded Programme on Immunization (EPI) vaccines, with the exception that the birth dose of oral polio vaccine is not required.
- Subjects who have not received a PCV booster following primary PCV series.
- Subject's parent must provide voluntary written informed consent for subject to participate in the study, is fully capable of comprehending and complying with study requirements and procedures, able and willing to return for all scheduled follow-up visits, and has expressed availability for the required study period, with access to a consistent means of telephone contact. An illiterate parent will require an impartial witness to be present during consenting process to include discussing the consent form, verbal consent and thumb-printing.
- Subjects who were not born premature, had a birth weight of > 2.5 kg, and who have a weight-to-height Z-score of ≥ -2 at the time of enrollment.
Exclusion Criteria:
- For Toddlers NOT enrolled in VAC-010 (PCV-primed only):
- Use of any investigational or non-registered drug within 90 days prior to screening, or planned during the course of study participation.
- Immunosuppression or immunodeficiency (inclusive of human immunodeficiency virus [HIV]) by medical history (inclusive of possible HIV through maternal fetal transfer at time of birth or through breast milk).
- Chronic, clinically significant pulmonary, cardiovascular, hepatobiliary, gastrointestinal, renal, neurological, or hematological functional abnormality or major congenital defects or illness that requires medical therapy, by medical history or clinical assessment. This includes abnormal vital signs as assessed by toxicity scoring.
- Any medical or social condition that in the opinion of the investigator may interfere with the study objectives, pose a risk to the study subject, or prevent the subject from completing the study.
- An employee (or first degree relative of employee) of the Sponsor, the Clinical Research Organization (CRO), the investigator or any site personnel.
- Disorders that required chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs within the 6 months prior to enrollment. An immunosuppressant dose of glucocorticoid will be defined as a systemic dose >10 mg of prednisone (adult dosage) adjusted for equivalent dosing in toddlers by weight. The use of topical glucocorticoids will be permitted.
- Administration of immunoglobulins and/or any blood products within the 6 months preceding enrollment in the study; or anticipation of such administration during the study period.
- History of meningitis, seizures or any neurological disorder.
- Subject who has evidence of congenital abnormality or developmental delay.
- Any evidence of fetal alcohol syndrome or history of alcohol abuse in mother during pregnancy.
研究計画
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
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PATH-wSP 300 µg + Booster
Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later.
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PATH-wSP 300 µg Only
Toddlers who enrolled in Cohort 1 of Study VAC-010 and received 300 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 300 µg PATH-wSP 8 weeks later.
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PATH-wSP 600 µg + Booster
Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP plus the two booster vaccines (Synflorix and Pentavac) followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later.
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PATH-wSP 600 µg Only
Toddlers who enrolled in Cohort 2 of Study VAC-010 and received 600 µg PATH-wSP and 2 saline injections followed by a 2nd injection of 600 µg PATH-wSP 8 weeks later.
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Booster Only (300 µg)
Toddlers who enrolled in Cohort 1 of Study VAC-010 and received one saline injection and the two booster vaccines (Synflorix and Pentavac) followed by a 2nd saline injection 8 weeks later.
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Booster Only (600 µg)
Toddlers who enrolled in Cohort 2 of Study VAC-010 and received one saline injection and the two booster vaccines (Synflorix and Pentavac) followed by a 2nd saline injection 8 weeks later.
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No Intervention (300 µg)
Toddlers who enrolled during Cohort 1 who did not participate in Study VAC-010 and did not receive either PATH-wSP or either of the booster vaccines (Pentavac or Synflorix).
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No Intervention (600 µg)
Toddlers who enrolled during Cohort 2 who did not participate in Study VAC-010 and did not receive either PATH-wSP or either of the booster vaccines (Pentavac or Synflorix).
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Prevalence of Streptococcus Pneumoniae in Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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The prevalence of Streptococcus pneumoniae (SPn) in the nasopharynx was measured by the number (and percentage) of participants positive for SPn detected by quantitative polymerase chain reaction (qPCR) from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Density of Streptococcus Pneumoniae in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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The density of Streptococcus pneumoniae (SPn) in the nasopharynx was measured by the number of autolysin (LytA) gene copies detected by quantitative polymerase chain reaction (qPCR) from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Geometric Mean Concentration (GMC) of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins
時間枠：Baseline (Week 0), 4 weeks post-vaccination 2 (Week 12), and 6 months post-vaccination 2 (Week 32).
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Immunogenicity was evaluated based on the following assays:
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Baseline (Week 0), 4 weeks post-vaccination 2 (Week 12), and 6 months post-vaccination 2 (Week 32).
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Geometric Mean Concentration Ratios of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins for PATH-wSP Groups Versus the Booster Only Group
時間枠：Week 32
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Data reported are the geometric mean concentration at 6 months post-vaccination 2 (Week 32) for each PATH-wSP group divided by the Booster (Synflorix and Pentavax)-only group (N=38). Immunogenicity was evaluated based on the following assays:
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Week 32
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Geometric Mean Fold Change of Immunoglobulin G (IgG) Antibodies Against Pneumococcal Proteins
時間枠：Baseline and Week 32
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Immunogenicity was evaluated based on the following assays:
The fold-change was calculated as the 6-month post-vaccination (Week 32) IgG response divided by the Baseline IgG response. |
Baseline and Week 32
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Percentage of Participants Meeting Seroresponse Fold-Rise Categories at 6 Months Post Vaccination 2
時間枠：Baseline and Week 32
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The percentage of participants with a seroresponse, defined as a ≥ 2, ≥ 3, and ≥ 4 fold-rise above Baseline in IgG antibody levels against Pneumococcal proteins. Fold-rise was calculated as the 6-month post-vaccination (Week 32) IgG response divided by the Baseline IgG level. Immunogenicity was evaluated based on the following assays:
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Baseline and Week 32
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Number of Participants With Neutralizing Antibody Response to Pneumolysin
時間枠：Baseline (Week 0) and 6 months post-vaccination 2 (Week 32)
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Neutralizing antibody responses to pneumolysin were assessed at Baseline and 6 months post vaccination 2 using an in vitro toxin neutralization assay that measures the ability of antibodies to neutralize wild-type pneumolysin-induced lysis of rabbit red blood cells. Each sample was categorized as negative (< 1/20 dilution) or positive (with titer between 1/20 and 1/320 dilution). Responses at higher dilutions indicate higher levels of neutralizing antibodies to pneumolysin. |
Baseline (Week 0) and 6 months post-vaccination 2 (Week 32)
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Number of Adverse Events (AE)
時間枠：32 weeks; for participants enrolled concurrently in Study VAC-010 adverse events were collected after the last VAC-010 visit through to Week 32.
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An AE was defined as any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, or laboratory or psychological/physiologic observations occurring in a person in a clinical study.
The AEs collected in this non-interventional study were those that remained open after the last visit in the VAC-010 Study, those attributed to study vaccine in VAC-010 with onset after the participant exited VAC-010, those that were related to a VAC-011 procedure (i.e.
blood draw, nasal swab sample), and all serious adverse events.
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32 weeks; for participants enrolled concurrently in Study VAC-010 adverse events were collected after the last VAC-010 visit through to Week 32.
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Prevalence of Streptococcus Pneumoniae Serotype 11A/D/E [11A] in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 11A/D/E [11A] is reported. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Prevalence of Streptococcus Pneumoniae Serotype 13 in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 13 is reported. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Prevalence of Streptococcus Pneumoniae Serotype 15A in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 15A is reported. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Prevalence of Streptococcus Pneumoniae Serotype 15B/C [15B] in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 15B/C [15B] is reported. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Prevalence of Streptococcus Pneumoniae Serotype 19A in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 19A is reported. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Prevalence of Streptococcus Pneumoniae Serotype 19F in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 19F is reported. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Prevalence of Streptococcus Pneumoniae Serotype 3 in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 3 is reported. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Prevalence of Streptococcus Pneumoniae Serotype 35B in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 35B is reported. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Prevalence of Streptococcus Pneumoniae Serotype 6A/B [6A] in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype 6A/B [6A] is reported. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Prevalence of Streptococcus Pneumoniae Serotype NT4b in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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Nasopharyngeal samples were further analyzed for the prevalence of specific Streptococcus pneumoniae serotypes by microarray. The number of participants with a positive result for SPn serotype NT4b is reported. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Density of Streptococcus Pneumoniae Serotype 11A/D/E [11A] in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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The density of Streptococcus pneumoniae serotype 11A/D/E [11A] in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Density of Streptococcus Pneumoniae Serotype 13 in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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The density of Streptococcus pneumoniae serotype 13 in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Density of Streptococcus Pneumoniae Serotype 15A in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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The density of Streptococcus pneumoniae serotype 15A in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Density of Streptococcus Pneumoniae Serotype 15B/C [15B] in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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The density of Streptococcus pneumoniae serotype 15B/C [15B] in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Density of Streptococcus Pneumoniae Serotype 19A in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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The density of Streptococcus pneumoniae serotype 19A in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Density of Streptococcus Pneumoniae Serotype 19F in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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The density of Streptococcus pneumoniae serotype 19F in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Density of Streptococcus Pneumoniae Serotype 3 in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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The density of Streptococcus pneumoniae serotype 3 in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Density of Streptococcus Pneumoniae Serotype 35B in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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The density of Streptococcus pneumoniae serotype 35B in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Density of Streptococcus Pneumoniae Serotype 6A/B [6A] in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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The density of Streptococcus pneumoniae serotype 6A/B [6A] in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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Density of Streptococcus Pneumoniae Serotype NT4b in the Nasopharynx
時間枠：Week 0, Week 12, Week 16, Week 20, Week 32
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The density of Streptococcus pneumoniae serotype NT4b in the nasopharynx was measured by the number of LytA gene copies detected by microarray from nasopharyngeal swabs taken at each study visit. NPC endpoints were analyzed within combined study groups:
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Week 0, Week 12, Week 16, Week 20, Week 32
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協力者と研究者
スポンサー
捜査官
- 主任研究者：Nekoye Otsyula, MB ChB MSc、Kenya Medical Research Institute/Walter Reed Project
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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